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mRNA Vaccines and Therapeutics

mRNA_121622A
[Messenger RNA (mRNA) - National Human Genome Research Institute, NIH]
 
 
 

- The Science Behind mRNA

Every virus has signature features on its surface that can trigger your immune system. Once the features are mapped, an mRNA vaccine provides the blueprint to create the defense that can help your body protect itself if it encounters the virus. 

Once your body has the blueprint, it knows exactly what to do. It reads mRNA strands to build a defense by producing antibody proteins that are a lot like the answer key to a test. This means the next time your immune system encounters this type of virus, it already has the answer to help protect you. 

Your body now knows how to neutralize the virus and is able to defend itself against the threat if it encounters the virus in the future. The message from the blueprint that was read is retained and recalled when needed. It’s like remembering the answer from an old test without having to re-learn the material. 

 

- Harnessing the Potential of mRNA

The rapid delivery of the world's first mRNA-based COVID-19 vaccine has brought the promise of mRNA technology into focus, but we believe the scientific community is only just beginning to realize its potential. The next wave of scientific innovation is upon us, and the scientific community is working hard to harness the power of mRNA. 

mRNA vaccines represent a promising alternative to traditional vaccine approaches due to their high potency, ability to be rapidly developed, and potential for low-cost manufacture and safe administration. However, until recently, their application was limited by the instability and inefficiency of mRNA delivery in vivo.

Recent technological advances have now largely overcome these issues, and multiple mRNA vaccine platforms against infectious diseases and several cancers have shown encouraging results in both animal models and humans. 

 

- mRNA Vaccines - A New Era in Vaccinology

Recent improvements to mRNA vaccines could increase protein translation, modulate innate and adaptive immunogenicity, and improve delivery. mRNA vaccines have elicited robust immunity against infectious disease targets in influenza, Zika, rabies and other animal models, especially in recent years using sequence-optimized mRNAs in lipid-encapsulated or naked forms. 

Multiple approaches to mRNA cancer vaccines, including dendritic cell vaccines and various types of directly injectable mRNA, have been used in many cancer clinical trials, with some promising results showing antigen-specific T cell responses and in some Prolonged disease-free survival.

Therapeutic considerations and challenges include scaling up Good Manufacturing Practice (GMP) manufacturing, developing regulations, further documenting safety and improving efficacy.

Important future research directions will be to compare and elucidate immune pathways activated by various mRNA vaccine platforms, improve existing approaches based on these mechanisms, and initiate new clinical trials against other disease targets.

 

- mRNA Therapeutics

The extraordinary success of mRNA vaccines against coronavirus disease 2019 (COVID-19) has reignited interest in mRNA as a means of delivering therapeutic proteins.

Early clinical trials of mRNA therapy include studies of paracrine vascular endothelial growth factor (VEGF) mRNA in heart failure and CRISPR-Cas9 mRNA in congenital liver-specific storage disease.

However, many challenges remain to be resolved before mRNA can be identified as a general therapeutic modality with broad relevance to rare and common diseases.

A range of new technologies are being developed to overcome these challenges, including methods to optimize mRNA cargo, lipid carriers with intrinsic tissue tropism, and in vivo transdermal delivery systems.

Judicious integration of these advances may open the prospect of biologically targeted mRNA therapeutics beyond vaccines and other immune stimulants for the treatment of multiple clinical indications.

 

 

[More to come ...]


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