Targeting lentiviral vector to specific cell types through surface displayed single chain antibody and fusogenic molecule.
Virol J
; 7: 35, 2010 Feb 11.
Article
en En
| MEDLINE
| ID: mdl-20149250
BACKGROUND: Viral delivery remains one of the most commonly used techniques today in the field of gene therapy. However, one of the remaining hurdles is the off-targeting effect of viral delivery. To overcome this obstacle, we recently developed a method to incorporate an antibody and a fusogenic molecule (FM) as two distinct molecules into the lentiviral surface. In this report, we expand this strategy to utilize a single chain antibody (SCAb) for targeted transduction. RESULTS: Two versions of the SCAb were generated to pair with our various engineered FMs by linking the heavy chain and the light chain variable domains of the anti-CD20 antibody (alphaCD20) via a GS linker and fusing them to the hinge-CH2-CH3 region of human IgG. The resulting protein was fused to either a HLA-A2 transmembrane domain or a VSVG transmembrane domain for anchoring purpose. Lentiviral vectors generated with either version of the SCAb and a selected FM were then characterized for binding and fusion activities in CD20-expressing cells. CONCLUSION: Certain combinations of the SCAb with various FMs could result in an increase in viral transduction. This two-molecule lentiviral vector system design allows for parallel optimization of the SCAb and FMs to improve targeted gene delivery.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Virales de Fusión
/
Lentivirus
/
Anticuerpos de Cadena Única
/
Tropismo Viral
/
Vectores Genéticos
Límite:
Humans
Idioma:
En
Revista:
Virol J
Asunto de la revista:
VIROLOGIA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido