Clinical pharmacology of siRNA therapeutics: current status and future prospects
| Autor: | Ahmed Khaled, Abosalha, Jacqueline, Boyajian, Waqar, Ahmad, Paromita, Islam, Merry, Ghebretatios, Sabrina, Schaly, Rahul, Thareja, Karan, Arora, Satya, Prakash |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Expert Review of Clinical Pharmacology. 15:1327-1341 |
| ISSN: | 1751-2441 1751-2433 |
| DOI: | 10.1080/17512433.2022.2136166 |
| Popis: | 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).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.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. |
| Databáze: | OpenAIRE |
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