Reconstituted influenza virus envelopes as an efficient carrier system for cellular delivery of small-interfering RNAs.
Gene Ther
; 13(5): 400-11, 2006 Mar.
Article
en En
| MEDLINE
| ID: mdl-16267567
Application of RNA interference for in vivo evaluation of gene function or for therapeutic interventions has been hampered by a lack of suitable delivery methods for small interfering RNA (siRNA). Here, we present reconstituted viral envelopes (virosomes) derived from influenza virus as suitable vehicles for in vitro as well as in vivo delivery of siRNAs. Virosomes are vesicles that bear in their membrane the influenza virus spike protein hemagglutinin (HA). This protein mediates binding of native virus to and fusion with cellular target membranes. Accordingly, virosomes with membrane-incorporated HA bind to cells, are taken up by receptor-mediated endocytosis, and fuse with the endosomal membrane to release their contents into the cytoplasm. When complexed to cationic lipids, siRNA was successfully encapsulated in virosomes. Virosomes with encapsulated siRNA fused with target membranes in a pH-dependent manner and delivered the encapsulated siRNA to several cell lines in vitro. Virosome-delivered siRNA markedly downregulated the synthesis of newly induced and constitutively expressed green fluorescent protein. Moreover, intraperitoneal injection of siRNA-loaded virosomes resulted in delivery of the nucleotides to cells in the peritoneal cavity. Our results indicate that virosomes are a promising delivery device for in vivo application, especially where topical administration of siRNA, for example, to the respiratory tract is envisaged.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Orthomyxoviridae
/
Terapia Genética
/
Virosomas
/
ARN Interferente Pequeño
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Gene Ther
Asunto de la revista:
GENETICA MEDICA
/
TERAPEUTICA
Año:
2006
Tipo del documento:
Article
País de afiliación:
Países Bajos
Pais de publicación:
Reino Unido