Design of siRNA Therapeutics from the Molecular Scale

Pharmaceuticals

Phillip Angart¹  Daniel Vocelle¹  Christina Chan¹ 

[1] Department of Chemical Engineering and Materials Science, Michigan State University, 428 S. Shaw Lane, Room 2527, East Lansing, MI 48824, USA;

关键词: siRNA therapeutic;    RNAi;    liver cancer;    siRNA design;    delivery vehicle design;   

DOI  :  10.3390/ph6040440

来源: mdpi

【 摘 要 】

While protein-based therapeutics is well-established in the market, development of nucleic acid therapeutics has lagged. Short interfering RNAs (siRNAs) represent an exciting new direction for the pharmaceutical industry. These small, chemically synthesized RNAs can knock down the expression of target genes through the use of a native eukaryotic pathway called RNA interference (RNAi). Though siRNAs are routinely used in research studies of eukaryotic biological processes, transitioning the technology to the clinic has proven challenging. Early efforts to design an siRNA therapeutic have demonstrated the difficulties in generating a highly-active siRNA with good specificity and a delivery vehicle that can protect the siRNA as it is transported to a specific tissue. In this review article, we discuss design considerations for siRNA therapeutics, identifying criteria for choosing therapeutic targets, producing highly-active siRNA sequences, and designing an optimized delivery vehicle. Taken together, these design considerations provide logical guidelines for generating novel siRNA therapeutics.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.