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cursor-pointer bg-darkBlue w-[40px] h-[40px] items-center justify-center before:content-[''] before:border-solid before:border-white before:border before:border-t-[0.11em] before:border-r-[0.11em] before:-rotate-45 before:w-[10px] before:h-[10px] before:border-b-0 before:border-l-0 z-50 before:absolute"></button></div></div></div><script id="__NEXT_DATA__" type="application/json">{"props":{"pageProps":{"post":{"title":"mRNA Technology: Is the Long Path Behind Leading to Endless Successes Ahead?","slug":"articles-mrna-technology-is-the-long-path-behind-leading-to-endless-successes-ahead","content":"\u003ch3\u003e\u003cspan style=\"color: #826464\"\u003eDecades of prior research, tremendous government funding, and unprecedented collaboration in the face of an urgent global health crisis made the success of messenger RNA (mRNA) vaccines against COVID-19 possible. Now that proof of concept has been realized, the industry is galvanized and hopeful that mRNA solutions can be developed for a wide range of previous undruggable disease targets from other infectious diseases to heart conditions and cancer.\u003c/span\u003e\u003c/h3\u003e\n\u003ch4 style=\"font-weight: normal\"\u003e\u003cspan style=\"color: #da5f5a\"\u003eYears of Hard Work and Fierce Dedication Came First\u003c/span\u003e\u003c/h4\u003e\n\u003cp\u003e\u003cspan\u003eThe concept of messenger RNA (mRNA) has been around since this form of RNA was first discovered in the early 1960s.\u003csup\u003e1\u003c/sup\u003e The first liposomal RNA constructs were prepared shortly thereafter, and before 1970 mRNA was shown to direct protein production in the lab setting. Synthetic mRNA was first produced in the laboratory in the mid-1980s, and shortly after that mRNA in cationic liposomes was delivered to human cells and shown to be biologically active. The first mRNA vaccines were developed in the early 1990s and tested in mice later that decade. \u003c/span\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003c!--more--\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eWork on mRNA as a vaccine stalled at this point, because it was seen as being too unstable and expensive.\u003csup\u003e1\u003c/sup\u003e Researchers were also finding that basic synthetic mRNA generally caused a strong and unacceptable inflammatory response.\u003csup\u003e2\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eSome interest remained in mRNA as a cancer immunotherapeutic, however. Researchers at Duke University had some success modifying patient cells with \u003c/span\u003esynthetic mRNA encoding for tumor proteins and then injecting those cells back into the patients to illicit a strong immune response. This approach ultimately failed, but at the time it drove the founding of CureVac and BioNTech, companies that hoped to inject mRNA directly into patients.\u003c/p\u003e\n\u003cp\u003eIt wasn’t until 2005\u003cspan\u003e, when, after years of unsuccessful efforts and a demotion, University of Pennsylvania researcher Katalin Karikó (now senior vice president at BioNTech), when\u003c/span\u003e collaborating with immunologist Drew Weissman on an mRNA vaccine for HIV/AIDs, identified the source of the inflammatory reaction and a means for avoiding it that involved replacing uridine nucleotides with pseudouridine.\u003csup\u003e1\u003c/sup\u003e So-called modified mRNA was then used by stem cell biologist Derrick Rossi (then at Boston Children’s Hospital) to transform skin cells into contracting muscle tissue via embryonic-like stem cells. Rossie was one of the cofounders of Moderna.\u003c/p\u003e\n\u003cp\u003eWhile these advances in RNA technology were being achieved, more progress was also being made in the field of liposomal drug delivery.\u003csup\u003e1\u003c/sup\u003e In the early 2000s, the first lipid nanoparticles (LNPs) comprising four different lipids were used to deliver DNA to cells, and by 2005 a scalable method for producing LNPs was established.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cdiv class=\"callout\"\u003e\n\u003cblockquote\u003e\n\u003ch4 class=\"callout-title\"\u003e\u003cspan style=\"color: #826464\"\u003eThe LNPs consist of four lipids, three of which provide the structure of the nanoparticle (a PEGylated lipid, cholesterol and phospholipid distearoylphosphatidylcholine (DSPC)). The fourth is an ionizable lipid with a positive charge that becomes neutral under physiological conditions, reducing the toxicity of the LNPs.\u003c/span\u003e\u003c/h4\u003e\n\u003c/blockquote\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThese advances combined led to the first clinical trials of LNP-based mRNA vaccines for infectious diseases in the 2015, as well as funding of mRNA vaccine research by the U.S. Defense Advanced Research Projects Agency (DARPA).\u003csup\u003e1\u003c/sup\u003e The first mRNA therapeutic (patisiran, ONPATTRO\u003csup\u003e®\u003c/sup\u003e, \u003cspan\u003eAlnylam Pharmaceuticals) received approval in the United States in 2018, and the first mRNA vaccines — against COVID-19 — were granted emergency use authorization in late 2020. \u003c/span\u003e\u003c/p\u003e\n\u003ch4 style=\"font-weight: normal\"\u003e\u003cspan style=\"color: #da5f5a\"\u003eSolving the Delivery Problem\u003c/span\u003e\u003c/h4\u003e\n\u003cp\u003eThe COVID-19 \u003cspan\u003emRNA vaccines from Moderna and BioNTech/Pfizer would not be possible without the development of an effective delivery technology. RNA molecules are much larger than small molecule drugs, and they carry a significant electric charge.\u003csup\u003e3\u003c/sup\u003e As a result, it is not easy for them to cross cell membranes. Getting mRNA to the right cells or tissues is also a major challenge. In addition, as mRNA molecules circulate in the blood, they are rapidly degraded by enzymes (RNases) in the body. \u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eLipid nanoparticles for drug delivery were developed by University of British Columbia, Vancouver, researcher Peter Cullis.\u003csup\u003e1\u003c/sup\u003e One of the companies he founded — Acuitas Therapeutics — provided the LNP technology for the BioNTech/Pfizer COVID-19 vaccine (Comirnaty\u003csup\u003e®\u003c/sup\u003e).\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eThe LNPs consist of four lipids, three of which provide the structure of the nanoparticle (a PEGylated lipid,\u0026nbsp;\u003c/span\u003e\u003cspan\u003echolesterol and phospholipid distearoylphosphatidylcholine (DSPC))\u003c/span\u003e\u003cspan\u003e.\u003csup\u003e4\u003c/sup\u003e The fourth is an ionizable lipid with a positive charge that becomes neutral under physiological conditions, reducing the toxicity of the LNPs.\u003csup\u003e1\u003c/sup\u003e The lipids protect the mRNA from degradation and help it enter cells.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eHowever, manufacturing the LNPs on a practical scale that would allow commercialization of mRNA vaccines formulated as LNPs was a stumbling block for a while.\u003csup\u003e1\u003c/sup\u003e The discovery that mixing a stream of lipids dissolved in alcohol with a stream of mRNA in an acidic buffer solution resulted in spontaneous formation of densely packed LNPs solved the issue. Novartis was the first company to use this technology to combine an mRNA vaccine and LNPs. \u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eSome companies are exploring other possible delivery technologies for mRNA, including polymer-based solutions and the use of conjugates, such as \u003cem\u003eN\u003c/em\u003e-acetylgalactosamine\u003c/span\u003e (GalNAc), that bind to specific receptors on the surfaces of cells.\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cdiv class=\"callout\"\u003e\n\u003cblockquote\u003e\n\u003ch4 class=\"callout-title\"\u003e\u003cspan style=\"color: #826464\"\u003eThe experience, knowledge, and capabilities both Moderna and BioNTech established developing mRNA vaccines against HIV/AIDs, influenza, and other diseases set both companies up to rapidly develop candidates against the novel coronavirus.\u003cbr /\u003e\u003c/span\u003e\u003c/h4\u003e\n\u003c/blockquote\u003e\n\u003c/div\u003e\n\u003ch4 style=\"font-weight: normal\"\u003e\u0026nbsp;\u003c/h4\u003e\n\u003ch4 style=\"font-weight: normal\"\u003e\u003cspan style=\"color: #da5f5a\"\u003eModerna and BioNTech Leading Commercialization Efforts\u003c/span\u003e\u003c/h4\u003e\n\u003cp\u003e\u003cspan\u003eBoth the founders of Moderna (Rossi, \u003c/span\u003eTimothy Springer, Robert Langer, and Noubar Afeyan)\u003cspan\u003e and the founders of BioNTech (\u003c/span\u003eUgur Sahin and his wife Özlem Türeci)\u003cspan\u003e, recognized the crucial value of the results achieved by \u003c/span\u003eKarikó and Weissman\u003cspan\u003e.\u003csup\u003e2\u003c/sup\u003e Both companies licensed the technology developed by the UPenn researchers.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eBioNTech sees itself not as an mRNA company but as \u003c/span\u003ean immunotherapy company and has largely pursued cancer vaccines based on its technology.\u003csup\u003e2\u003c/sup\u003e It initially stayed out of the limelight, but steadily made progress, publishing nearly 150 scientific papers and establishing numerous deals with Big Pharma firms. The company didn’t go public until 2020 but already has multiple clinical trials underway. By that time, it was also working on an mRNA vaccine against influenza.\u003c/p\u003e\n\u003cp\u003eModerna started out as an mRNA therapy company and went out of its way to attract attention and stay in the public eye.\u003csup\u003e2\u003c/sup\u003e It garnered significant financial backing even before any of its work was published, raising more than $1 billion by 2015.\u003csup\u003e1\u003c/sup\u003e When it could not overcome unwanted immune responses at the higher doses required for its therapeutic candidates, the company had to switch its focus to vaccines, a move that disappointed investors. Even so, the company was able to advance nine mRNA vaccine candidates for infectious diseases into clinical trials.\u003c/p\u003e\n\u003cp\u003eWhen the COVID-19 pandemic arrived, both Moderna and BioNTech were well positioned to pursue an mRNA \u003cspan\u003evaccine solution.\u003c/span\u003e\u003c/p\u003e\n\u003ch4 style=\"font-weight: normal\"\u003e\u003cspan style=\"color: #da5f5a\"\u003eCoronavirus Ideal Target for First Commercial mRNA Success\u003c/span\u003e\u003c/h4\u003e\n\u003cp\u003e\u003cspan\u003eBy early 2020, the advances achieved in LNP drug delivery for mRNA, the prior approval of some mRNA therapies, and the experience gained by companies like Moderna and BioNTech during development of their mRNA vaccine candidates meant that the pieces were in place to facilitate the success of the first mRNA vaccines. The unprecedented levels of government funding\u003csup\u003e5\u003c/sup\u003e and extensive cross-industry collaboration, both driven by the urgency of the pandemic, accelerated the technology to the point where its commercialization was possible.\u003csup\u003e6\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eThe experience, knowledge, and capabilities both Moderna and BioNTech established developing mRNA vaccines against HIV/AIDs, influenza, and other diseases set both companies up to rapidly develop candidates against the novel coronavirus. They also benefited from tremendous advances in sequencing technology, previous in-depth research on other troubling coronaviruses, including SARS and MERS, and advanced algorithms capable of rapidly identifying optimal stable molecular structures for mRNA vaccines.\u003csup\u003e7\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eOnce the sequence of the SARS-CoV-2 virus was known, it didn’t take either company long to develop several candidates and select the most promising ones. These were sent off for clinical studies using established networks positioned to rapidly recruit participants.\u003csup\u003e7\u003c/sup\u003e While the clinical trials were underway, commitments by governments to purchase millions of doses, plus direct funding assistance, made it possible for manufacturing capacity to be established in advance of efficacy confirmation, both in-house and through partnerships with contract development \u003c/span\u003e\u003cspan\u003eand manufacturing organizations (CDMOs)\u003csup\u003e5\u0026nbsp;\u003c/sup\u003e— a scenario impossible to imagine pre-pandemic.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eModerna elected to pursue the development of its COVID-19 mRNA vaccine on its own. BioNTech, however, determined that it needed a manufacturing partner.\u003csup\u003e5\u003c/sup\u003e Pfizer was an obvious choice, because the two companies were already working together on the development of mRNA influenza vaccines. Notably, Pfizer did not take any upfront government funding, ensuring that the company remained free from politics and bureaucracy.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eThe success of the COVID-19 mRNA vaccines is raising significant excitement in the field, both for other mRNA vaccines and therapeutics. The commercialization of these vaccines did take place, however, under unique circumstances that the world hopes not to experience again. Some of the challenges for mRNA drug products have not yet been truly overcome. For mRNA therapeutics, targeted cell delivery remains an issue, as does dose optimization and immunogenicity.\u003csup\u003e8\u003c/sup\u003e Both therapeutics and vaccines face high costs, some of which are due to the cold-chain challenges that face these unstable materials. Regulatory guidelines have advanced somewhat during the pandemic, but some uncertainties still remain in this regard as well.\u003c/span\u003e\u003c/p\u003e\n\u003cdiv class=\"callout\"\u003e\n\u003cblockquote\u003e\n\u003ch4 class=\"callout-title\"\u003e\u003cspan style=\"color: #826464\"\u003emRNA vaccines and therapies can be produced with high specific molecular designs and functionalities, allowing the targeting of a wide range of biologic mechanisms involved in many different diseases.\u003c/span\u003e\u003c/h4\u003e\n\u003c/blockquote\u003e\n\u003c/div\u003e\n\u003ch4 style=\"font-weight: normal\"\u003e\u003cspan style=\"color: #da5f5a\"\u003ePotentially Limitless Potential\u003c/span\u003e\u003c/h4\u003e\n\u003cp\u003e\u003cspan\u003emRNA technology is highly promising for a number of reasons. Vaccines and therapies can be produced with high specific molecular designs and functionalities, allowing the targeting of a wide range of biologic mechanisms involved in many different diseases.\u003csup\u003e8\u003c/sup\u003e\u0026nbsp;Furthermore, because mRNA \u003c/span\u003edelivers instructions to cells regarding protein production, it is unlike other existing types of drugs and\u003cspan\u003e can be used to target intracellular proteins, which have previously been considered undruggable using traditional small molecule and antibody-based drugs.\u003csup\u003e9\u003c/sup\u003e\u003c/span\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eIn fact, any cellular molecules that are produced using RNA forms can be targeted. Similarly, mRNA can potentially be used to target most pathogens.\u003csup\u003e9\u003c/sup\u003e As a result, mRNA technologies can theoretically be used where \u003c/span\u003eimmune-related responses are required, such as in vaccines for infectious diseases and cancer, but also where missing or altered proteins are the cause of a disease.\u003csup\u003e6\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eIndeed, the fact that mRNA drugs can address underlying causes of diseases means they may have the potential to achieve greater efficacy than traditional drugs.\u003csup\u003e10\u003c/sup\u003e In addition, with the advanced state of genome sequencing, personalized mRNA therapies and vaccines can be developed for specific patients. The rapid degradation of mRNA also reduces concerns about undesired genomic integration.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003eManufacturing advantages exist as well. Platform approaches are applicable; only the genetic sequence changes, and manufacturing, purification, and LNP formation are generally the same processes.\u003csup\u003e9\u003c/sup\u003e As importantly, mRNA is produced using a chemical synthesis process, not a biological cell culture process, making it easier to scale.\u003csup\u003e10 \u003c/sup\u003eBeyond that, a strong manufacturing network for mRNA — and much of the necessary regulatory framework — were both largely established as the result of the success of the COVID-19 vaccines.\u003csup\u003e11\u003c/sup\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003eInitial mRNA development efforts focused on rare genetic diseases, such as Usher syndrome type 2 and Hurler’s syndrome, but today candidates are undergoing clinical trials for more common conditions, including cancer and cardiovascular disease, as well as vaccines for many different infectious diseases.\u003csup\u003e8\u003c/sup\u003e By late summer 2021, there were over 1800 clinical studies involving mRNA listed on ClinicalTrials.gov, nearly one quarter of which were in phase II.\u003csup\u003e10\u003c/sup\u003e Approximately 60% of the pipeline are oncology therapies for solid tumors, and 30% are vaccines against infectious diseases.\u003csup\u003e6\u003c/sup\u003e\u0026nbsp;The remaining candidates cover a wide range of diseases with varying disease mechanisms, including the production of hormones or cytokines. Some specific examples include treatments for colorectal cancer and Lyme disease, cures for autoimmune diseases, and nonviral delivery systems for gene therapies.\u003csup\u003e12\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eSome of the biggest projects are targeting the development of vaccines for infectious diseases that have to date eluded effective vaccine solutions, including malaria, influenza, and HIV/AIDS. The speed of development and the ability to encode for multiple variants in one vaccine are driving this interest.\u003csup\u003e13 \u003c/sup\u003eDevelopment speed is also crucial for many of the cancer vaccines in development, for which genetic analysis data for individual patient tumors is used to produce personalized mRNA vaccines for each that are administered after surgery to generate an immune response against those tumor cells for years to come.\u003c/p\u003e\n\u003cp\u003eToday, both BioNTech and Moderna have extensive clinical pipelines that include both mRNA vaccines and therapeutics. Other companies are developing targeted mRNA candidates by putting the mRNA into viruses or non-viral particles that are only taken up by certain cells or using polymers that are absorbed only by certain tissues.\u003csup\u003e10\u003c/sup\u003e There also some companies that, rather than produce mRNA, are developing small molecule drugs that regulate mRNA activity.\u003c/p\u003e\n\u003cp\u003eThe latter approach is one way to overcome some of the challenges faced by mRNA vaccines and therapeutics. While LNPs address the instability and cellular uptake issues associated with mRNA to some degree, they are not a complete solution, and research is ongoing to improve both aspects.\u003csup\u003e8\u003c/sup\u003e Immunogenicity problems and off-target effects, while largely not observed with the COVID-19 vaccines, are still observed with many mRNA candidates, and more work must be done in this area. In general, better understanding of the biology of mRNA and its specific roles in various diseases is needed.\u003csup\u003e6\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eBeyond the scientific challenges, the rate of advance achieved for mRNA technology during the COVID-19 pandemic is unlikely to be repeated, because there are no longer unprecedented levels of government funding and collaboration occurring in the field.\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eEven so, there is tremendous excitement in the biopharma industry about the arguably limitless potential of mRNA technology to enable the development of vaccines and therapeutics that will address significant unmet medical needs. The market is expected to expand at double-digit growth rates over the next 5 years.\u003csup\u003e14,15\u003c/sup\u003e Estimates for the value of the global mRNA therapeutic and vaccine market differ significantly, however. IMARC Group predicts that it will expand at a CAGR of 10.5% from $9.41 billion in 2021 to $15.49 billion by 2026.\u003csup\u003e14\u003c/sup\u003e BCC Research, meanwhile, pegs the value at \u003c/span\u003e$46.7 billion in 2021 and rising at a CAGR of 16.8% to $101.3 billion by 2026.\u003csup\u003e15\u003c/sup\u003e\u003c/p\u003e\n\u003ch4 style=\"font-weight: normal\"\u003e\u003cspan style=\"color: #da5f5a\"\u003eRevitalizing the Vaccine Sector \u003c/span\u003e\u003c/h4\u003e\n\u003cp\u003e\u003cspan\u003eBefore the COVID-19 pandemic, investment in the development of new vaccines was quite limited.\u003csup\u003e16\u003c/sup\u003e Vaccines had become commoditized, and most biopharma companies had little incentive to invest time and money into the development of new products. The arrival of the COVID-19 pandemic underscored this short-sightedness on the parts of both governments and the industry.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eThe success of the two mRNA vaccines against the SARS-CoV-2 virus has, in effect, led to the birth of a new vaccine sector. Traditional vaccine formulations contained live, inactivated, or dead virus. While some vaccines are still produced in this manner, the majority of newer products are based on engineered proteins that represent the portions of viruses that illicit immune responses. These vaccines take less time to produce — 3–4 years versus 8–10, but still require production via cell culture or fermentation, or in the case of traditional influenza vaccines, chicken eggs.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eAs was seen with the COVID-19 vaccines, the simpler and platformable nature of mRNA technology allows for the development of new vaccines in much less time. Once the desired genetic sequence is known, candidates for preclinical and clinical studies can be generated within a few months.\u003csup\u003e17\u003c/sup\u003e The ability to produce candidates quickly, including candidates that can induce immune responses against multiple strains of a virus, means that more options can be screened, increasing the likelihood of creating an optimum vaccine. \u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eThere is also hope that further advances in mRNA technology could reduce the timeline for commercialization of mRNA vaccines even further.\u003csup\u003e17\u003c/sup\u003e For instance, DARPA announced in March 2021 that it awarded $41 million to GE Research in Niskayuna, New York; the Broad Institute, Cambridge, Massachusetts; and the University of Washington, Seattle, to develop a manufacturing platform that will allow companies to quickly produce new mRNA vaccines. Separately, Wellcome Leap, a UK charity, is providing $60 million in funding to help enable standardized manufacturing of mRNA.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eIn addition to the leaders BioNTech, Moderna, and CureVac, big pharma companies, such as Pfizer, Sanofi, GSK, and AstraZeneca, as well as numerous startups, are focusing on the development of mRNA vaccines for a wide range of infectious diseases.\u003csup\u003e5\u003c/sup\u003e In August 2021, Sanofi acquired Translate Bio for $3.2 billion,\u003csup\u003e21\u003c/sup\u003e a move that followed an announcement earlier in the summer that the company would invest $475 million annually in a new “mRNA Center of Excellence.”\u003csup\u003e22\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003ePharma Intelligence (part of Informa) counted a total of 49 mRNA prophylactic vaccine candidates that remained in clinical development in October 2021.\u003csup\u003e5\u003c/sup\u003e Moderna is responsible for 13 clinically active candidates alone. Several companies are developing mRNA vaccines against influenza and HIV/AIDs. \u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eDeveloping an HIV vaccine has been unsuccessful to date, because current vaccine technology does not allow for the production of vaccines with sufficiently broad neutralizing antibodies against HIV. mRNA might offer a solution. \u003c/span\u003eIAVI and Scripps Research, along with Moderna and other collaborators, have developed mRNA vaccine candidates that look like the HIV env structure and can induce specific immature B cells to develop broadly neutralizing antibodies.\u003csup\u003e23\u003c/sup\u003e An initial clinical study found the vaccines (mRNA 1644 and mRNA 1644v2) safe, and a clinical trial has been initiated to determine if they can safely generate broadly neutralizing antibodies in healthy adults.\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eInterest in developing a successful flu vaccine is high, because the current options typically are no more than 60% effective and often as low as 30% due to the nature of the vaccine technology employed.\u003csup\u003e11 \u003c/sup\u003emRNA technology would allow vaccines to be developed more quickly, leaving less time for virus mutation. The ultimate goal is a universal vaccine that would work on all variants and make it possible to need only one shot every several years.\u003c/span\u003e\u003c/p\u003e\n\u003cdiv class=\"callout\"\u003e\n\u003cblockquote\u003e\n\u003ch4 class=\"callout-title\"\u003e\u003cspan style=\"color: #826464\"\u003eDevelopment speed is also crucial for many of the cancer vaccines in development, for which genetic analysis data for individual patient tumors is used to produce personalized mRNA vaccines for each that are administered after surgery to generate an immune response against those tumor cells for years to come.\u003c/span\u003e\u003c/h4\u003e\n\u003c/blockquote\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cspan\u003eFlu vaccine maker Seqirus (a \u003c/span\u003ebusiness of CSL Limited)\u003cspan\u003e, which produces vaccines using both eggs and cells, recently announced that is has created \u003c/span\u003ea dedicated program to\u003cspan\u003e develop next-generation self-amplifying mRNA (sa-mRNA) vaccines.\u003csup\u003e24\u003c/sup\u003e The company is developing a number of s\u003c/span\u003ea-mRNA–based influenza vaccine candidates, with preclinical results demonstrating promise as compared to more traditional influenza vaccine technologies and hopes to have seasonal and pandemic influenza vaccine candidates in the second half of 2022. Unlike regular mRNA, sa-mRNA instructs the body to replicate mRNA, amplifying the amount of protein made, thus providing the same response levels at reduced dosage or stronger cellular responses and higher antibody titers at the same dose levels.\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003ePfizer, meanwhile, announced in late September 2021 that the first \u003c/span\u003eparticipants have been dosed in a phase I clinical trial to evaluate the safety, tolerability, and immunogenicity of a single-dose quadrivalent mRNA vaccine against influenza in healthy adults.\u003csup\u003e25\u003c/sup\u003e The company has been partnering with BioNTech for several years on the flu vaccine.\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eMalaria is another important target, because this disease has presented challenges due to the complex and evolving nature of the organism that causes it.\u003csup\u003e18,19\u003c/sup\u003e Rabies, which is invariably fatal, is also of significant interest. Initial clinical data for CureVac’s mRNA candidate have shown it to be safe and to produce a strong immune response.\u003csup\u003e19\u003c/sup\u003e There is also hope that an mRNA vaccine might be developed for tuberculosis.\u003csup\u003e20\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eOrganizations such as the Bill \u0026amp; Melinda Gates Foundation and the Coalition for Epidemic Preparedness Innovations (CEPI) are also funding research efforts focused on the development of mRNA vaccines for infectious diseases that have not received much interest in recent years, such as dengue or Lassa fever.\u003csup\u003e11\u003c/sup\u003e Other targets include Nipah, Zika, herpes, and hepatitis, plus several more.\u003c/span\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003ch4 style=\"font-weight: normal\"\u003e\u003cspan style=\"color: #da5f5a\"\u003eProviding Personalized/Precision Cancer Therapies\u003c/span\u003e\u003c/h4\u003e\n\u003cp\u003e\u003cspan\u003eImmuno-oncology drugs aim to teach our immune systems how to recognize cancer cells as foreign and then to destroy them. The numerous cancer immunotherapy drugs that have received marketing authorization have demonstrated the effectiveness of this approach. These treatments, however, still only work for a portion of the patients.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eCancer vaccines that encode specific genetic mutations within a given patient’s tumor could potentially train immune cells to target tumor cells bearing those mutations. Generally, \u003c/span\u003esurface exposed antigens, such as tumor-associated antigens (TAA) including differentiation antigens, overexpressed antigens, and cancer/testis antigens, and truly tumor-specific antigens (TSAs), such as viral and mutated neoantigens, are targeted.\u003csup\u003e26\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003em\u003c/span\u003eRNA provides for an effective means of antigen delivery in combination with innate immune activation–mediated co-stimulation.\u003csup\u003e26\u003c/sup\u003e\u0026nbsp;Approaches include mRNA-based dendritic cell vaccines, mRNA-encoded antigen receptors, mRNA-encoded antibodies, and mRNA-encoded immunomodulators, such as cytokines and stimulatory ligands and receptors.\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eWith a platform manufacturing approach, mRNA is making this type of oncology treatment practically possible.\u003csup\u003e27\u0026nbsp;\u003c/sup\u003eBioNTech recently announced that it had dosed the first patient in a \u003c/span\u003ephase II clinical study of its personalized mRNA cancer vaccine BNT122 in colorectal cancer.\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eEven for more common cancers, it may be possible to develop targeted mRNA vaccines.\u003csup\u003e27\u003c/sup\u003e For instance, a large percentage of patients with lung cancer have tumors that the \u003c/span\u003ecarcinoembryonic antigen, and mRNA vaccines can be extremely sensitive for this biomarker. Such a treatment could be invaluable for patients whose lung cancer is not diagnosed until the disease is well advanced, which is often the case for patients that develop lung cancer due to exposure to asbestos.\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eStartup Strand Therapeutics is one company developing sa-mRNA treatments for solid tumors based on technology development at MIT.\u003csup\u003e28\u003c/sup\u003e The firm has demonstrated in animal studies that its technology can \u003c/span\u003eregulate the timing and level of protein expression and expects to begin human clinical studies in 2022 with funding from BeiGene. In general, the therapy is programmed to enter a tumor, detect relevant mutations, and prompt an immune response to those specific mutations. Such a therapy would be allogeneic (or off-the-shelf) rather than patient-specific, as is the case with chimeric antigen receptor (CAR) T cell therapies, and without the risk of cytokine-release syndrome, according to the company.\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eResearchers at \u003c/span\u003eMemorial Sloan Kettering Cancer Center believe that mRNA could provide significant hope to patients with pancreatic cancer.\u003csup\u003e29\u003c/sup\u003e Pancreatic cancer is difficult to treat, often because it is not caught until the tumor has significantly advanced. Immunotherapy is promising, because, for the few patients who do survive, their removed tumors tend to have large numbers of T cells owing to the presence of special neoantigens that trigger an immune response. These neoantigens also circulate in the blood up to 12 years following removal of the tumor. mRNA vaccines are an attractive means for delivering these specialized neoantigens to patients who do not naturally generate them. After surgery to remove the tumor, the tumor is generically sequenced, and the mutations that produce the optimum neoantigen proteins are identified. A checkpoint inhibitor is administered to the patient while an mRNA vaccine specific to these proteins is manufactured. The hope is that, once administered, these personalized cancer vaccines will attack any remaining or newly formed tumor cells.\u003c/p\u003e\n\u003cp\u003eBeyond cancer vaccines, the versatility of mRNA is allowing for the exploration of a wider range of cancer immunotherapies based on this technology.\u003csup\u003e26\u003c/sup\u003e With the ability during the chemical synthesis of mRNA to modify structural elements and to pursue various delivery approaches, it is now possible to do much more. mRNA is even being used to produce CAR-T cells with better safety profiles, and the first mRNA-encoded cytokine therapies are being evaluated in the clinic. The success of the COVID-19 vaccines has, as is the case with the traditional vaccine sector, opened up significant new opportunities for mRNA cancer therapeutics due to the greater knowledge and understanding gained, the establishment of manufacturing know-how and capacity, and the forging of regulatory \u003cspan\u003epathways.\u003c/span\u003e\u003c/p\u003e\n\u003ch4 style=\"font-weight: normal\"\u003e\u003cspan style=\"color: #da5f5a\"\u003eDelivering CRISPR Gene-Editing Technology\u003c/span\u003e\u003c/h4\u003e\n\u003cp\u003e\u003cspan\u003eGene editing has tremendous promise for expanding the spectrum of diseases that can be treated with more traditional gene therapies because it allows for the addition, removal, or editing of specific genetic information. One challenge, though, is getting the gene editing tools into the right cells. mRNA is an attractive delivery vehicle. \u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eIn the summer of 2021, researchers at the U.K.’s Royal Free Hospital, funded by Intellia Therapeutics and Regeneron, used mRNA to deliver CRISPR gene-editing technology that could permanently treat the rare genetic disease transthyretin amyloidosis and demonstrated for the first time in human clinical trials that CRISPR can treat genetic disorders in humans.\u003csup\u003e30\u003c/sup\u003e mRNA was used to specifically deliver the gene-editing instructions to the liver. The result is exciting, because there are many more diseases of the liver that could be treated with this type of technology. It could also, with modifications, be used to delivery gene-editing solutions for diseases of other tissues, including bone marrow, nervous system, and muscle diseases.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eSeparately in the summer of 2021, \u003c/span\u003eCRISPR pioneer Feng Zhang, Ph.D., of the Broad Institute and colleagues developed a new mRNA delivery system that harnesses a human retrovirus-like protein.\u003csup\u003e31\u003c/sup\u003e Referred to as SEND, the system leverages the ability of a human protein called PEG10 to bind to its own mRNA and form\u0026nbsp;a protective capsule around it. The PEG10 is engineered, focusing on the minimal sequences required to trigger efficient packaging and functional transfer of the mRNA, to carry RNA cargoes. Fusogen proteins are also added to facilitate the fusion to cells for efficient transfer of the genomic material, in this case CRISPR-Cas9 gene editing tools, to specific cells.\u003c/p\u003e\n\u003cp\u003eIn their first attempts, the researchers achieved 60% insertions and deletions in recipient mouse cells and 40% edits at a specific\u0026nbsp;location on a chromosome in human cells.\u003csup\u003e31\u003c/sup\u003e Because PEG10 is naturally produced in the body, the likelihood that immunogenic responses will occur is reduced. In addition, unlike viral vector delivery systems, this mRNA approach leveraging a human protein should theoretically allow repeated dosing, which would expand the applications for nucleic acid therapies.\u003c/p\u003e\n\u003ch4 style=\"font-weight: normal\"\u003e\u003cspan style=\"color: #da5f5a\"\u003eTackling Major Conditions\u003c/span\u003e\u003c/h4\u003e\n\u003cp\u003e\u003cspan\u003eWhile the first targets for mRNA have generally been rare diseases, academic researchers and biopharma companies of all sizes are increasingly exploring the potential for mRNA therapy to address more common diseases affecting much larger patient populations. The success of the COVID-19 vaccines and the establishment of commercial production infrastructure and a regulatory pathway have created even more interest.\u003c/span\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eAs outlined above, mRNA medicines can be used to replace defective genes and/or proteins, express enzymes that can correct defective genes in cell therapy via transfection of the mRNA into the cells \u003cem\u003eex vivo\u003c/em\u003e to \u003c/span\u003eenhance cell survival, proliferation and/or function, and to enable the generation of new mAbs, among other applications.\u003c/p\u003e\n\u003cp\u003eOne area of research is the generation of induced pluripotent stem cells (iPSCs), which are attractive alternatives to embryonic stem cells.\u003csup\u003e32\u003c/sup\u003e While viral vectors have commonly been used to generate IPSCs from terminally differentiated adult somatic cells (e.g., skin fibroblasts), there is a risk of genomic integration. Most alternatives that avoid this risk exhibit low efficiencies with respect to ISPC generation. Different mRNA methods, however, produced ISPCs with acceptable efficiency and with reduced mutations compared with viral vector–generated cells.\u003c/p\u003e\n\u003cp\u003eIndeed, mRNA has been used to directly generate a variety of different therapeutic cells and/or enhance their proliferation, survival, or function.\u003csup\u003e32\u003c/sup\u003e For instance, mRNA has been transfected into somatic cells to directly generate cardiovascular cells \u003cem\u003eex vivo\u003c/em\u003e. mRNA has also been transfected into mesenchymal stromal cells (MSCs), which have numerous attractive properties, including the capability to self-renew, to differentiate into different cell lineages, and to migrate to sites of injury and secrete proteins that reduce inflammation and promote tissue repair.\u003c/p\u003e\n\u003cdiv class=\"callout\"\u003e\n\u003cblockquote\u003e\n\u003ch4 class=\"callout-title\"\u003e\u003cspan style=\"color: #826464\"\u003eApproaches include mRNA-based dendritic cell vaccines, mRNA-encoded antigen receptors, mRNA-encoded antibodies, and mRNA-encoded immunomodulators, such as cytokines and stimulatory ligands and receptors.\u003c/span\u003e\u003c/h4\u003e\n\u003c/blockquote\u003e\n\u003c/div\u003e\n\u003cp\u003eThis approach is being explored as a means for increasing the therapeutic potency and homogeneity of the cells by modulating their migratory and adhesion properties to ensure targeted delivery. One potential application is the treatment of vascular senescence (aging), which contributes to atherosclerotic processes, with MSCs transfected with mRNA encoding for human telomerase (\u003cspan\u003eTERT\u003c/span\u003e). In addition, researchers have found that a new mRNA therapeutic (codon-optimized, UTR-modified, HPLC-purified mRNA telomerase in lipid nanoparticles) for the corre\u003cspan\u003ection of endotheliopathy, which underlies many cardiovascular disorders and other age-related diseases. \u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eBoth of these examples involve \u003cem\u003eex vivo\u003c/em\u003e modification of cells followed by administration of the modified cells to the patient. In some cases, direct injection of mRNA therapies may be appropriate.\u003csup\u003e32\u003c/sup\u003e\u0026nbsp;For instance, intramyocardial injection of mRNA therapies has been shown in mice to lead to cardiac regeneration, improved heart function, and greater long-term survival when administered during induced coronary artery ligation. These results have led to initiation of a clinical trial of an mRNA therapeutic for cardiac regeneration by AstraZeneca (AZD8601) in collaboration with Moderna. Several other mRNA therapeutics targeting different molecular pathways are also under development.\u003c/span\u003e\u003c/p\u003e\n\u003ch4 style=\"font-weight: normal\"\u003e\u003cspan style=\"color: #da5f5a\"\u003eMarket Dominated by Specialists, but Big Pharma Moving In\u003c/span\u003e\u003c/h4\u003e\n\u003cp\u003e\u003cspan\u003eFor companies to be active in the mRNA market, they must have access to specialized technology and expertise, either in-house or through partnerships. Currently, the smaller companies that were built specifically to develop mRNA-based therapeutics and vaccines —BioNTech and Moderna — are the true specialists in the field and have the lead, with numerous candidates progressing through the clinic in addition to their approved COVID-19 vaccines.\u003csup\u003e8\u003c/sup\u003e CureVac is another company in this category. \u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eBig pharma companies generally appear to prefer to partner with such smaller specialist firms. Pfizer’s collaboration with BioNTech is a great example. So is AstraZeneca’s work with Moderna and GSK’s partnership with CureVac. Sanofi, which ended up not being a player in the COVID-19 vaccine race, has taken a more active approach with its acquisition of long-term partner Translate Bio to bring specialist capabilities in-house.\u003csup\u003e21\u003c/sup\u003e Merck, meanwhile, acquired AmpTec, a mRNA contract development and manufacturing organization (CDMO) in early 2021.\u003csup\u003e33\u003c/sup\u003e AmpTec leverages a unique polymerase chain reaction (PCR)-based technology for mRNA manufacturing that builds on Merck’s expertise in lipids manufacturing, allowing the company to provide a unique and integrated offering across the mRNA value chain.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eThe success of the COVID-19 vaccines is driving both acquisition and investment interest in many other small and emerging biotechs focused on mRNA. Approximately 12 companies other than Moderna and BioNTech are developing mRNA therapeutics and vaccines.\u003csup\u003e34\u0026nbsp;\u003c/sup\u003eReCode Therapeutics raised $80 million in series B financing from the likes of Pfizer and Sanofi, among others.\u003csup\u003e35\u003c/sup\u003e The money will be used to fund phase I trials of mRNA candidates in cystic fibrosis and primary ciliary dyskinesia, another lung disease. \u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eArcturus Therapeutics is another company working on cystic fibrosis, as is Sanofi through Translate Bio. Arcturus recently announced that it has acquired an exclusive license from Alexion Pharmaceuticals to certain patent-pending inventions relating to nucleic acid purification technologies.\u003csup\u003e36\u003c/sup\u003e As mentioned above, Strand Therapeutics is focused on cancer treatments for solid tumors.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eCompanies in the mRNA value chain are also making headlines with \u003c/span\u003e\u003cspan\u003eSPAC (\u003c/span\u003e\u003cspan\u003eSpecial Purpose Acquisition Corporation) deals, a way of going public without going through an initial public offering. \u003c/span\u003e\u003cspan\u003eGreenLight Biosciences\u003c/span\u003e\u003cspan\u003e, which produces mRNA via fermentation rather than chemical synthesis, participated in a \u003c/span\u003e\u003cspan\u003e$1.5 billion \u003c/span\u003e\u003cspan\u003emerger with SPAC Environmental Impact Acquisition Corp.\u003csup\u003e37\u003c/sup\u003e According to the company, its natural, biological approach disrupts traditional manufacturing bottlenecks. GreenLight is developing a COVID-19 vaccine and vaccines for seasonal flu and sickle-cell disease. It also is involved in the agrochemical and other markets. Gingko Bioworks, a synthetic biology company that has developed a new manufacturing approach to mRNA (\u003cem\u003evide infra\u003c/em\u003e) became a public company through a $17.5 billion SPAC merger with Soaring Eagle Acquisition Corp.\u003csup\u003e38\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ch4 style=\"font-weight: normal\"\u003e\u003cspan style=\"color: #da5f5a\"\u003eOngoing Development and Manufacturing Advances\u003c/span\u003e\u003c/h4\u003e\n\u003cp\u003e\u003cspan\u003eAlthough the COVID-19 vaccines were developed and commercialized in record time, there are still opportunities for improvement of mRNA therapeutic and vaccine designs and the manufacturing processes used to produce them. \u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eResearchers at King’s College London are aiming to develop very small, cartridge-based mRNA manufacturing systems as part of a U.K. government–funded project called the Future Vaccine Manufacturing Research Hub.\u003csup\u003e11\u003c/sup\u003e Such systems could be used to produce vaccines in hospitals to provide local manufacturing at low cost and to eliminate cold-chain issues.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eThe delivery of mRNA drugs could also be improved so that intramuscular shots may not be necessary. The hope of some, including leading mRNA researcher Karikó, is development of the ability to manipulate mRNA so that is can only enter certain cells, last longer, and in general make delivery more precise and less toxic and thus more effective.\u003csup\u003e11\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eGingko Bioworks and partner Aldevron say they have made a step in the right direction, achieving a “breakthrough” in mRNA manufacturing that increases production yields of the vaccinia capping enzyme (VCE), which helps the body recognize foreign mRNA and thus prevent its degradation, by more than 10-fold.\u003csup\u003e39\u003c/sup\u003e Aldevron has acquired exclusive rights to the process. Notably, Gingko had previously partnered with Moderna on process optimization for raw materials used to make its mRNA vaccines. \u003c/span\u003e\u003cspan\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eThe U.S. government is also partnering with the biopharma industry to address immediate vaccine needs overseas and domestically and to prepare for future pandemics.\u003csup\u003e40\u003c/sup\u003e In addition to investing in additional manufacturing capacity for COVID-19 mRNA vaccines, the program is intended to ensure the United States is prepared for future pandemics caused by different viruses so that sufficient quantities of vaccines can be produced in a matter of months. The public–private partnership will carry a price tag in the billions. That includes new solutions for mRNA manufacturing.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003e\u003cimg src=\"https://thatsnice-testing3.com/legacy/2022_Q1/PA_Q122_feature_sidebar.png\" alt=\"PA_Q122_feature_sidebar\" width=\"1492\" loading=\"lazy\" style=\"width: 1492px;margin-left: auto;margin-right: auto\"\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ch4 style=\"font-weight: normal\"\u003e\u003cspan style=\"color: #da5f5a\"\u003eSo Where is mRNA Really Headed?\u003c/span\u003e\u003c/h4\u003e\n\u003cp\u003e\u003cspan\u003eAll of the investment and activity around mRNA vaccines and therapeutics driven by the success of the COVID-19 vaccines from BioNTech/Pfizer and Moderna is certainly exciting. But there is still great uncertainty as to whether mRNA will be applicable for the prevention and treatment of other diseases. Yes, some clinical trials have been promising, but mRNA candidates have been in development for many years, yet not one — other than the COVID-19 vaccines — has received regulatory authorization.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eAt this point, it isn’t known whether the success achieved with the SARS-CoV-2 vaccines will be repeatable for other infectious diseases or whether mRNA immuno-oncology treatments, especially if they require personalized solutions, such as with autologous CAR-T-cell therapies, and other therapeutics will be achievable with practical dosing schedules and no undesired immunogenicity. \u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eThere are plenty of people who believe that mRNA will be a hugely successful sector within the biopharma industry. Indeed, mRNA startups, largely in the United States and Europe, raised approximately $4.6 billion in funding in recent months.\u003csup\u003e6 \u003c/sup\u003eThese companies, as well as BioNTech and Moderna, which are expected to reap billions of profits from their COVID-19 vaccines, will funnel these monies into their pipeline candidates.\u003csup\u003e34\u003c/sup\u003e The hope is that that some of these potential new vaccines and therapeutics will help meet the tremendous unmet medical need that exists across a broad range of diseases, both rare and widespread. We certainly hope — for the sake of these many, many patients — that mRNA turns out to be truly transformative.\u003c/span\u003e\u003c/p\u003e\n\u003ch4 style=\"font-weight: normal\"\u003eReferences\u003c/h4\u003e\n\u003col\u003e\n\u003cli\u003e\u003cspan style=\"color: #000000\"\u003e \u003cstrong\u003eDolgin, Elie.\u003c/strong\u003e “The tangled history of mRNA vaccines\u003cstrong\u003e.” \u003c/strong\u003e\u003cem\u003eNature\u003c/em\u003e. 597: 318–324 (2021). \u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan style=\"color: #000000\"\u003e \u003ca href=\"https://www.statnews.com/staff/damian-garde/\" style=\"color: #000000\"\u003e\u003cstrong\u003eGarde\u003c/strong\u003e\u003c/a\u003e\u003cstrong\u003e, Damian \u003c/strong\u003e\u003cstrong\u003eand Jonathan Saltzman.\u003c/strong\u003e “The story of mRNA: How a once-dismissed idea became a leading technology in the Covid vaccine race.” STAT News. 10 Nov.2020.\u0026nbsp; \u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan style=\"color: #000000\"\u003e \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Kim%20YK%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=32509554\" style=\"color: #000000\"\u003e\u003cstrong\u003eKim\u003c/strong\u003e\u003c/a\u003e\u003cstrong\u003e, Young-Kook. \u0026#8220;\u003c/strong\u003eRNA Therapy: Current Status and Future.\u003cstrong\u003e\u0026#8221; \u003c/strong\u003e\u003cspan style=\"font-weight: normal\"\u003eC\u003cem\u003ehonnam \u003c/em\u003e\u003cem\u003eMed\u003c/em\u003e\u003cem\u003e J.\u003c/em\u003e\u003c/span\u003e 56: 87–93 (2020). \u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003e\u003cspan\u003eMacdonald, Gareth.\u003c/span\u003e\u003c/strong\u003e \u003cspan\u003eHow Research from the ’70s, ’80s, and ’90s Drove mRNA Vaccine Development,” \u003cem\u003eBioProcess Insider eBook: Vaccines Revisited — The Past, Present, and Future of Nucleic-Acid Vaccine Production\u003c/em\u003e. 16 Nov.\u003c/span\u003e\u0026nbsp;2021.\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003e\u003cspan\u003eNelson, Millie.\u003c/span\u003e\u003c/strong\u003e \u003cspan\u003e“The Moderna Era: The Past, Present, and Future of mRNA Vaccines,” \u003cem\u003eBioProcess Insider eBook: \u003c/em\u003e\u003cem\u003eVaccines Revisited — The Past, Present, and Future of Nucleic-Acid Vaccine Production.\u003c/em\u003e 16 Nov. 2021.\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003e\u003cspan\u003eHeiber, Isabelle and Elias Eckert.\u003c/span\u003e\u003c/strong\u003e\u003cspan\u003e “How mRNA medicines might change the drug landscape,” Ernst \u0026amp; 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\u003cem\u003eNature.\u003c/em\u003e 598: S30-S31 (2021). \u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003e\u003cspan\u003eBarna, Mark.\u003c/span\u003e\u003c/strong\u003e\u003cspan\u003e “mRNA technology showing promise for range of diseases: COVID-19 vaccine spurs more research.” \u003cem\u003eThe Nation\u0026#8217;s Health.\u003c/em\u003e 51: 1-8 (2021). \u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan style=\"color: #000000\"\u003e\u003ca href=\"https://www.chemistryworld.com/clare-sansom/1237.bio\" style=\"color: #000000\"\u003e\u003cstrong\u003eSansom\u003c/strong\u003e\u003c/a\u003e\u003cstrong\u003e, Clare. \u0026#8220;\u003c/strong\u003e mRNA vaccines for Covid and beyond.\u003cspan style=\"font-weight: normal\"\u003e\u0026#8221; \u003cem\u003eChemistry World. \u003c/em\u003e25 Oct. 2021. \u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan style=\"color: #000000\"\u003e\u003ca href=\"https://www.devex.com/news/authors/1576248\" style=\"color: #000000\"\u003e\u003cstrong\u003eChakamba\u003c/strong\u003e\u003c/a\u003e\u003c/span\u003e\u003cstrong\u003e\u003cspan\u003e\u003cspan style=\"color: #000000\"\u003e, Rum\u003c/span\u003ebi. \u0026#8220;\u003c/span\u003e\u003c/strong\u003e\u003cspan\u003eIs mRNA technology a game changer for global health?\u003c/span\u003e\u003cspan style=\"font-weight: normal\"\u003e\u003cem\u003e\u0026#8221; Devex News.\u003c/em\u003e 25 May 2021.\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan\u003e\u003cstrong\u003eCross, Ryan.\u003c/strong\u003e\u003c/span\u003e\u003cspan\u003e “\u003c/span\u003e\u003cspan\u003eSanofi is all in on mRNA, with $3.2 billion Translate Bio acquisition\u003c/span\u003e\u003cspan\u003e.”\u003cem\u003e Chemical \u0026amp; Engineering News (C\u0026amp;EN).\u003c/em\u003e 3 \u003c/span\u003e\u003cspan\u003eAug. 2021. \u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cem\u003e\u003cspan\u003eSanofi launches dedicated vaccines mRNA Center of Excellence\u003c/span\u003e\u003c/em\u003e\u003cspan\u003e. Sanofi. 29 Jun. 2021. \u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan\u003e\u003cstrong\u003eScherer\u003c/strong\u003e\u003c/span\u003e\u003cstrong\u003e\u003cspan\u003e, \u003c/span\u003e\u003c/strong\u003e \u003cspan\u003e“Human Trials for HIV Vaccine Created With mRNA Technology to Begin.” WebMD. 2 Sep. 2021. \u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cem\u003e\u003cspan\u003eSeqirus Announces Investment in Next-Generation Influenza Vaccine Technology, Self-Amplifying Messenger RNA (sa-mRNA).\u003c/span\u003e\u003c/em\u003e\u003cspan\u003e 19 Aug. 2021.\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan\u003e\u003cem\u003ePfizer Starts Study of mRNA-Based Next Generation Flu Vaccine Program.\u003c/em\u003e\u003c/span\u003e\u003cspan\u003e 27 Sep. 2021. \u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003e\u003cspan\u003eBeck, Jan D. et al.\u003c/span\u003e\u003c/strong\u003e\u003cspan\u003e “mRNA therapeutics in cancer im\u003cspan style=\"color: #000000\"\u003emunotherapy\u003c/span\u003e\u003c/span\u003e\u003cspan style=\"color: #000000\"\u003e.” \u003cem\u003eMolecular Cancer.\u003c/em\u003e 20:\u0026nbsp;69 (2021). \u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan style=\"color: #000000\"\u003e\u003ca href=\"https://www.pharmexec.com/authors/jonathan-sharp\" style=\"color: #000000\"\u003e\u003cstrong\u003eSharp\u003c/strong\u003e\u003c/a\u003e\u003cstrong\u003e, Jonathan. \u0026#8220;\u003c/strong\u003e mRNA Technology: First COVID-19, Now Cancer\u003cspan style=\"font-weight: normal\"\u003e.\u0026#8221; \u003cem\u003ePharmaceutical Executive\u003c/em\u003e. 22 Oct. 2021. \u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003e\u003cspan\u003eVinluan, Frank.\u003c/span\u003e\u003c/strong\u003e\u003cspan\u003e “mRNA startup Strand Therapeutics lands $52M to “program” new cancer therapies.” \u003cem\u003eMed City News.\u003c/em\u003e 23 Jun. 2021. \u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan\u003e“\u003c/span\u003e\u003cspan\u003eCan mRNA Vaccines Fight Pancreatic Cancer? MSK Clinical Researchers Are Trying to Find Out\u003c/span\u003e\u003cspan\u003e.” \u003cem\u003eMemorial Sloan Kettering Cancer Center\u003c/em\u003e. 31 May \u003c/span\u003e2021.\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003e\u003cspan\u003eDucharme\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan\u003e, \u003c/span\u003e\u003c/strong\u003e\u003cspan\u003e\u003c/span\u003e\u003cspan\u003e “MRNA\u0026#8217;s Next Chapter Has Nothing to Do With COVID-19 Vaccines.\u003c/span\u003e” \u003cem\u003eTime.\u003c/em\u003e 2 \u003cspan\u003eAug. 2021. \u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003e\u003cspan\u003eLiu, Angus.\u003c/span\u003e\u003c/strong\u003e\u003cspan\u003e “CRISPR pioneer Feng Zhang\u0026#8217;s latest work delivers mRNA, gene therapy with a human protein.” \u003cem\u003eFierce Biotech\u003c/em\u003e. 19 Aug. 2021. \u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003e\u003cspan\u003eChanda, Palas K., Roman Sukhovershin, and John P. Cooke.\u003c/span\u003e\u003c/strong\u003e\u003cspan\u003e “mRNA-Enhanced Cell Therapy and Cardiovascular Regeneration.” \u003cem\u003e10:\u003c/em\u003e 187 (2021). \u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cem\u003e\u003cspan\u003eMerck Acquires AmpTec to Expand mRNA Capabilities for Vaccines, Treatments and Diagnostics.\u003c/span\u003e\u003c/em\u003e\u003cspan\u003e Merck. 7 Jan. 2021. \u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003e\u003cspan\u003eArmstrong, Annalee.\u003c/span\u003e\u003c/strong\u003e\u003cspan\u003e “The mRNA era has arrived thanks to COVID-19. What\u0026#8217;s next in the pipeline?” \u003cem\u003eFierce Biotech\u003c/em\u003e. 1 Sep. 2021. \u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003e\u003cspan\u003eLaHucik, Kyle.\u003c/span\u003e\u003c/strong\u003e\u003cspan\u003e “Another $80M: mRNA biotech ReCode matches 2020 series A with Pfizer, Sanofi money for cystic fibrosis trial.” \u003cem\u003eFierce Biotech. \u003c/em\u003e21 Oct. 2021. \u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cem\u003e\u003cspan\u003eArcturus Therapeutics Acquires Exclusive License to mRNA Manufacturing Technology from Alexion Pharmaceuticals.\u003c/span\u003e\u003c/em\u003e\u003cspan\u003e Arcturus Therapeutics. 22 Feb. 2021. \u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003e\u003cspan\u003eGoodwin, Kate.\u003c/span\u003e\u003c/strong\u003e\u003cspan\u003e “mRNA Disruptor Goes Public in $1.5 Billion SPAC Deal.” \u003cem\u003eBiospace\u003c/em\u003e. 10 Aug. 2021. \u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan\u003e“Synbio Powerhouse Ginkgo Bioworks Goes Public in $17.5B SPAC Deal.” \u003cem\u003e Eng. News.\u003c/em\u003e 11 May 2021\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003e\u003cspan\u003eKansteiner, Fraiser.\u003c/span\u003e\u003c/strong\u003e\u003cspan\u003e “Ginkgo and Aldevron tout mRNA manufacturing \u0026#8216;breakthrough\u0026#8217;—and the perks could stretch well beyond COVID-19, exec says.” \u003cem\u003eFierce Pharma\u003c/em\u003e. 10 Aug. 2021. \u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003e\u003cspan\u003eStolberg\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan\u003e, \u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan\u003eSheryl Gay.\u003c/span\u003e\u003c/strong\u003e\u003cspan\u003e “The U.S. aims to lift Covid vaccine manufacturing to create a billion doses a year.” \u003cem\u003eNew York Times.\u003c/em\u003e 17 Nov. 2021. \u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003e\u003cspan\u003eBoada Christian et al.\u003c/span\u003e\u003c/strong\u003e\u003cspan\u003e “The Limitless Future of RNA Therapeutics.” \u003cem\u003e Bioeng. Biotechnol\u003c/em\u003e. 18 Mar. 2021.\u003c/span\u003e\u003c/li\u003e\n\u003c/ol\u003e\n","date":"2022-03-23T15:37:15","dateGmt":"2022-03-23T19:37:15","roundtable":{"topic":null,"question":null,"roundtable":null},"featuredImage":{"node":{"sourceUrl":"https://thatsnice-testing3.com/wp-content/uploads/PA_Q122_feature_banner.jpg"}},"articleTags":{"edges":[{"node":{"name":"COVID-19 Vaccine","slug":"covid-19-vaccine","id":"dGVybToxMjI3OQ=="}},{"node":{"name":"Features","slug":"features","id":"dGVybTo5MTQ1"}},{"node":{"name":"Immunotherapy","slug":"immunotherapy","id":"dGVybTo5NzUy"}},{"node":{"name":"mRNA Manufacturing","slug":"mrna-manufacturing","id":"dGVybToxMjU4NQ=="}},{"node":{"name":"mRNA Therapeutic","slug":"mrna-therapeutic","id":"dGVybToxMjU2OA=="}},{"node":{"name":"mRNA Vaccine","slug":"mrna-vaccine","id":"dGVybToxMjI5Mw=="}},{"node":{"name":"Q1 2022","slug":"q1-2022","id":"dGVybToxMjc0OA=="}},{"node":{"name":"Research and Clinical Development","slug":"research-and-clinical-development","id":"dGVybToxMDM3OQ=="}},{"node":{"name":"RNA Therapies","slug":"rna-therapies","id":"dGVybToxMTgzNQ=="}}]},"mainTopic":{"mainTopic":"Column: Technology"},"articleFields":{"articleId":"PAO-03-022-NI-02","accentColor":"#da5f5a","vimeoId":null,"associatedCompanies":null,"authors":[{"author":{"id":"cG9zdDo3OTc2OA==","title":"Cynthia A. Challener, Ph.D.","slug":"cynthia-a-challener-ph-d","featuredImage":{"node":{"sourceUrl":"https://thatsnice-testing3.com/wp-content/uploads/C_Challener_TN.webp"}},"authorFields":{"bio":"\u003cp\u003eDr. Challener is an established industry editor and technical writing expert in the areas of chemistry and pharmaceuticals. She writes for various corporations and associations, as well as marketing agencies and research organizations, including That’s Nice and Nice Insight.\u003c/p\u003e\n","email":"cynthia.c@thatsnice.com","linkedin":"http://www.linkedin.com/in/cynthiachallener","title":"Scientific Content Director","company":{"id":"cG9zdDo3NzEwNA==","title":"Pharma’s Almanac","slug":"pharmas-almanac"}}}}]}},"vimeoThumb":false},"__N_SSG":true},"page":"/articles/[slug]","query":{"slug":"articles-mrna-technology-is-the-long-path-behind-leading-to-endless-successes-ahead"},"buildId":"3j1kwQFJR4bAVxAE0sM1B","isFallback":false,"gsp":true,"scriptLoader":[]}</script></body></html>