The impact of unprotected T cells in RNAi-based gene therapy for HIV-AIDS.
Mol Ther
; 22(3): 596-606, 2014 Mar.
Article
en En
| MEDLINE
| ID: mdl-24336172
ABSTRACT
RNA interference (RNAi) is highly effective in inhibiting human immunodeficiency virus type 1 (HIV-1) replication by the expression of antiviral short hairpin RNA (shRNA) in stably transduced T-cell lines. For the development of a durable gene therapy that prevents viral escape, we proposed to combine multiple shRNAs against highly conserved regions of the HIV-1 RNA genome. The future in vivo application of such a gene therapy protocol will reach only a fraction of the T cells, such that HIV-1 replication will continue in the unmodified T cells, thereby possibly frustrating the therapy by generation of HIV-1 variants that escape from the inhibition imposed by the protected cells. We studied virus inhibition and evolution in pure cultures of shRNA-expressing cells versus mixed cell cultures of protected and unprotected T cells. The addition of the unprotected T cells indeed seems to accelerate HIV-1 evolution and escape from a single shRNA inhibitor. However, expression of three antiviral shRNAs from a single lentiviral vector prevents virus escape even in the presence of unprotected cells. These results support the idea to validate the therapeutic potential of this anti-HIV approach in appropriate in vivo models.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Replicación Viral
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ARN Viral
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Linfocitos T
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Síndrome de Inmunodeficiencia Adquirida
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VIH-1
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Lentivirus
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ARN Interferente Pequeño
Tipo de estudio:
Guideline
Límite:
Humans
Idioma:
En
Año:
2014
Tipo del documento:
Article