Latest Development on RNA-Based Drugs and Vaccines

Abstract

Drugs and vaccines based on mRNA and RNA viruses show great potential and direct translation in the cytoplasm eliminates chromosomal integration. Limitations are associated with delivery and stability issues related to RNA degradation. Clinical trials on RNA-based drugs have been conducted in various disease areas. Likewise, RNA-based vaccines for viral infections and various cancers have been subjected to preclinical and clinical studies. RNA delivery and stability improvements include RNA structure modifications, targeting dendritic cells and employing self-amplifying RNA. Single-stranded RNA viruses possess self-amplifying RNA, which can provide extreme RNA replication in the cytoplasm to support RNA-based drug and vaccine development. Although oligonucleotide-based approaches have demonstrated potential, the focus here is on mRNA- and RNA virus-based methods.

mRNA as a Transformative Technology for Vaccine Development to Control Infectious Diseases

“…However, optimization of RNA structural elements and formulation can increase antigen expression and durability. 43 The cap (often a cap 1 structure 15,[44][45][46], UTRs, and the poly(A) tail are crucial for stability of the mRNA molecule, accessibility to ribosomes, and interaction with the translation machinery, [47][48][49][50] therefore representing targets for optimization (reviewed in Ross, 43 Lundstrom, 51 and Sahin et al 52 ). Additionally, codon usage can have a beneficial impact on protein translation, and replacing rare codons with frequently used synonymous codons is a common practice to enhance protein expression from DNA, RNA, and viral vector vaccines.…”

The solid progress of nanomedicine

“…Moreover, a promising shift within the nanomedicine research community is the additional focus on cardiovascular [29], autoimmune [30,31], neurological [32], infectious [33], and genetic and rare diseases [34]. RNA-based synthetic vaccines are another emerging area with high potential for nanomedicine [35][36][37]. Hence, public and private science funders and policy makers should drive such diversification to stimulate the pursuit of nanomedicines for clinical applications beyond cancer.…”

DNA and RNA Vaccines: Current Status, Quality Requirements and Specific Aspects of Preclinical Studies

“…Добавление UTR, содержащих различные регуляторные элементы, используется для повышения эффективности трансляции и повышения стабильности мРНК. Например, введение 3′-UTR гена α-глобина или 5′-, 3′-UTR гена β-глобина стабилизирует мРНК [24,26,28]. В случаях необходимости быстрой деградации мРНК в 3′-UTR могут включаться элементы, богатые аденин-урацил последовательностями [29].…”

“…Еще одним способом «улучшить» свойства мРНК-вакцин является использование химически модифицированных нуклеотидов. Например, включение модифицированного псевдоуридина повышает стабильность и трансляцию РНК, также включение химически модифицированных нуклеотидов приводит к снижению иммуногенности векторов [28].…”