Clinical pharmacology of siRNA therapeutics: current status and future prospects.
Expert Rev Clin Pharmacol
; 15(11): 1327-1341, 2022 Nov.
Article
in En
| MEDLINE
| ID: mdl-36251525
ABSTRACT
INTRODUCTION:
Small interfering RNA (siRNA) has emerged as a powerful tool for post-transcriptional downregulation of multiple genes for various therapies. Naked siRNA molecules are surrounded by several barriers that tackle their optimum delivery to target tissues such as limited cellular uptake, short circulation time, degradation by endonucleases, glomerular filtration, and capturing by the reticuloendothelial system (RES). AREAS COVERED This review provides insights into studies that investigate various siRNA-based therapies, focusing on the mechanism, delivery strategies, bioavailability, pharmacokinetic, and pharmacodynamics of naked and modified siRNA molecules. The clinical pharmacology of currently approved siRNA products is also discussed. EXPERT OPINION Few siRNA-based products have been approved recently by the Food and Drug Administration (FDA) and other regulatory agencies after approximately 20 years following its discovery due to the associated limitations. The absorption, distribution, metabolism, and excretion of siRNA therapeutics are highly restricted by several obstacles, resulting in rapid clearance of siRNA-based therapeutic products from systemic circulation before reaching the cytosol of targeted cells. The siRNA therapeutics however are very promising in many diseases, including gene therapy and SARS-COV-2 viral infection. The design of suitable delivery vehicles and developing strategies toward better pharmacokinetic parameters may solve the challenges of siRNA therapies.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
COVID-19
Limits:
Humans
Language:
En
Journal:
Expert Rev Clin Pharmacol
Year:
2022
Type:
Article
Affiliation country:
Canada