APR January/February 2022 - 72

» FORMULATION AND DEVELOPMENT
»
Future Trends in mRNA Technology
The success of mRNA vaccines provides the potential to launch a
second " Golden Age of Medicine. " Given its expedited manufacturing
properties and " plug and play " platform structure, mRNA technology
likely will become the mainstay of epidemic and pandemic rapid
response in both the vaccine and therapeutic medicine realms.
The ability of the mRNA vaccine backbone to be conserved while
swapping out the mRNA sequence that codes one pathogenic protein
for another means that multicomponent vaccines targeting several
different strains within one virus family - and universal vaccines
targeting multiple medical conditions - have become an exciting
possibility. Although it is tempting to assume that mRNA technology
will eventually supplant all other vaccine platforms, we need to
acknowledge that not every vaccine technology will work for every
target, and uncertainties and questions remain surrounding long-term
immune response durability of mRNA vaccines.
Applying the technology to therapeutic indications in the fields
of immuno-oncology, rare disease, protein replacement or
supplementation, and cell and gene therapy is not science fiction - it
is the active pursuit of many leading mRNA biotechnology companies.
Optimizing and modulating delivery and expression of mRNA to meet
the dosing needs of a therapeutic as opposed to a vaccine, will lead
the way to wider applicability of this modality.
Gene therapy for metabolic diseases, heart disease and immunooncology
are currently in the pipeline of the major biopharmaceutical
companies that are developing mRNA therapeutics. In this application
of the technology, mRNA is administered to the patient to compensate
for a defective gene or protein, or to supply a therapeutic protein.
In addition, mRNA technology can be used to enhance cell therapy.
The mRNA is transfected into ex vivo cells to alter the cell phenotype
or function, and then these cells are reintroduced into the patient to
treat the underlying disease. Clinical trials of mRNA-enhanced cell
therapy are currently in progress for the treatment of melanoma and
myasthenia gravis.
Overcoming activation of the innate immune system, which is a boon
for mRNA vaccines, also will be key to honing mRNA therapeutics
where immune activation is counterproductive. Newer biotech
companies are on the cutting edge of this revolutionary frontier by
creatively reimagining the structure - and hence expression - of
mRNA for therapeutics.7
Conclusion
6.
Groundbreaking mRNA technology has ushered in an exciting chapter
in the history of medicine. There are clear advantages of mRNA
technology in the vaccine field, especially in a pandemic setting, while
research gaps still exist in optimizing the technology and expanding
its use beyond vaccines. Other mRNA technologies also will add to the
breadth of new approaches. The research community has only begun
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| January/February 2022
7.
to explore the potential applications of mRNA technology, but the
possibilities are inspiring with future breakthroughs expected.
Author Biographies
Vanessa Elharrar, MD, MPH, is Vice President, PPD Clinical
Research Services, Thermo Fisher Scientific. With more
than 16 years of clinical research experience, she serves as
the vaccines business strategy lead. Trained in preventive
medicine and public health, she is passionate about public health-focused
research and has worked on more than 30 clinical trials.
Martina Kovac, MD, is Vice President, PPD Clinical Research
Services, Thermo Fisher Scientific. In this role, she provides
medical and scientific expertise with a focus on vaccine
development strategies across various therapeutic areas,
including strategic medical leadership and oversight of global vaccine
development programs. She has expertise leading large cross-functional
vaccine development teams and has led programs with external
collaborators in cross-cultural environments.
Anusha Streubel, MD, MPH is Executive Medical Director,
PPD Clinical Research Services, Thermo Fisher Scientific. As
part of the global product development vaccines team, she
provides medical and scientific expertise, with a focus on
clinical development strategies. She has provided medical leadership,
expertise and oversight for multiple vaccine development programs,
specializing in mRNA technology across therapeutic areas in both
pediatric and adult populations.
References
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" Positive aspects of the mRNA platform for SARS-CoV-2 vaccines. " Hum Vaccin Immunother
2021; 17(8):2445-2447. Accessed at: https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC8040488/.
" mRNA vaccines for infectious diseases: Principles, delivery and clinical translation. "
Chaudhary N, Weissman D, Whitehead KA. Nature Reviews Drug Discovery. 20:817-7838
(2021). Accessed at: https://www.nature.com/articles/s41573-021-00283-5.
" mRNA vaccines manufacturing: Challenges and bottlenecks. " Rosa SS, Prazeres DMF,
Azevedo AM. Vaccine. 2021 Apr 15; 39(16):2190-2200. Accessed at: https://pubmed.ncbi.
nlm.nih.gov/33771389/.
" Addressing the Cold Reality of mRNA Vaccine Stability. " Crommelin DJA, Anchordoquy TJ,
Volkin DB et all. J Pharm Sci 110(3):997-1001, March 2021. Accessed at: https://pubmed.
ncbi.nlm.nih.gov/33321139/.
" Development and Licensure of Vaccines to Prevent COVID-19: Guidance for Industry. "
U.S. Department of Health and Human Services, Food and Drug Administration, Center
for Biologics Evaluation and Research. June 2020. Accessed at https://www.fda.gov/
media/139638/download.
" WHO global vaccine safety multi-country collaboration project on safety in pregnancy:
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Vaccine. December 2021. Accessed at https://www.sciencedirect.com/science/article/pii/
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040488/ https://www.nature.com/articles/s41573-021-00283-5 https://pubmed.ncbi.nlm.nih.gov/33771389/ https://pubmed.ncbi.nlm.nih.gov/33321139/ https://www.fda.gov/media/139638/download https://www.sciencedirect.com/science/article/pii/S2590136221000401?via%3Dihub# https://www.nature.com/articles/nrd4278

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