Pharmaceutical Research

, Volume 27, Issue 3, pp 400–420

Pseudovirions as Vehicles for the Delivery of siRNA

Authors

  • Paul E. Lund
    • Laboratory of Cell Biology, National Cancer InstituteNational Institutes of Health
  • Ryan C. Hunt
    • Center for Biologics Evaluation and ResearchFood and Drug Administration
  • Michael M. Gottesman
    • Laboratory of Cell Biology, National Cancer InstituteNational Institutes of Health
    • Center for Biologics Evaluation and ResearchFood and Drug Administration
Expert Review

DOI: 10.1007/s11095-009-0012-2

Cite this article as:
Lund, P.E., Hunt, R.C., Gottesman, M.M. et al. Pharm Res (2010) 27: 400. doi:10.1007/s11095-009-0012-2

Abstract

Over the last two decades, small interfering RNA (siRNA)-mediated gene silencing has quickly become one of the most powerful techniques used to study gene function in vitro and a promising area for new therapeutics. Delivery remains a significant impediment to realizing the therapeutic potential of siRNA, a problem that is also tied to immunogenicity and toxicity. Numerous delivery vehicles have been developed, including some that can be categorized as pseudovirions: these are vectors that are directly derived from viruses but whose viral coding sequences have been eliminated, preventing their classification as viral vectors. Characteristics of the pseudovirions discussed in this review, namely phagemids, HSV amplicons, SV40 in vitro-packaged vectors, influenza virosomes, and HVJ-Envelope vectors, make them attractive for the delivery of siRNA-based therapeutics. Pseudovirions were shown to deliver siRNA effector molecules and bring about RNA interference (RNAi) in various cell types in vitro, and in vivo using immune-deficient and immune-competent mouse models. Levels of silencing were not always determined directly, but the duration of siRNA-induced knockdown lasted at least 3 days. We present examples of the use of pseudovirions for the delivery of synthetic siRNA as well as the delivery and expression of DNA-directed siRNA.

Key words

pseudoviral delivery vehiclepseudovirionsiRNA delivery

Copyright information

© US Government 2009