Pseudovirions as vehicles for the delivery of siRNA.
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.
Lund
Paul E
PE
Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Hunt
Ryan C
RC
Gottesman
Michael M
MM
Kimchi-Sarfaty
Chava
C
D000818:Animals; D006801:Humans; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D022701:Virosomes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014780:Viruses / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D034741:RNA, Small Interfering; D022701:Virosomes