Regulatory guidelines and preclinical tools to study the biodistribution of RNA therapeutics.
Adv Drug Deliv Rev
; 184: 114236, 2022 05.
Article
in English
| MEDLINE | ID: covidwho-1757033
ABSTRACT
The success of the messenger RNA-based COVID-19 vaccines of Moderna and Pfizer/BioNTech marks the beginning of a new chapter in modern medicine. However, the rapid rise of mRNA therapeutics has resulted in a regulatory framework that is somewhat lagging. The current guidelines either do not apply, do not mention RNA therapeutics, or do not have widely accepted definitions. This review describes the guidelines for preclinical biodistribution studies of mRNA/siRNA therapeutics and highlights the relevant differences for mRNA vaccines. We also discuss the role of in vivo RNA imaging techniques and other assays to fulfill and/or complement the regulatory requirements. Specifically, quantitative whole-body autoradiography, microautoradiography, mass spectrometry-based assays, hybridization techniques (FISH, bDNA), PCR-based methods, in vivo fluorescence imaging, and in vivo bioluminescence imaging, are discussed. We conclude that this new and rapidly evolving class of medicines demands a multi-layered approach to fully understand its biodistribution and in vivo characteristics.
Keywords
BLI; Biodistribution; Comirnatmy; Distribution; FISH; FLI; Givlaari; Givosiran; Guidelines; Imaging; Inclisiran; LNP; Leqvio; Lipid nanoparticle; Lumasiran; MS; Mass spectrometry; Moderna; Onpattro; Oxlumo; Patisiran; Pfizer/BioNTech; QWBA; RNA therapeutic; RT-qPCR; Regulatory; Spikevax; Vaccine; bDNA; mRNA; mRNA vaccine; siRNA
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
COVID-19 Vaccines
/
COVID-19
Topics:
Vaccines
Limits:
Humans
Language:
English
Journal:
Adv Drug Deliv Rev
Journal subject:
Pharmacology
/
Drug Therapy
Year:
2022
Document Type:
Article
Affiliation country:
J.addr.2022.114236
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