A conditionally replicating HIV-based vector that stably expresses an antiviral shRNA against HIV-1 replication.
Mol Ther
; 14(2): 268-75, 2006 Aug.
Article
em En
| MEDLINE
| ID: mdl-16697708
ABSTRACT
Human pathogenic viruses can be targeted by therapeutic strategies based on RNA interference. Whereas the administration of synthetic short interfering RNAs (siRNAs) may transiently inhibit viral replication, long-term inhibition may be achieved through stable intracellular expression of siRNAs or short hairpin RNAs (shRNAs). Both approaches face serious problems with delivery to the right cells in an infected individual. We explored the potential of a replicating HIV-based vector to deliver an antiviral shRNA cassette into HIV-1-susceptible target cells to block chronic HIV-1 infection. The vector is based on a doxycycline (dox)-dependent HIV-1 variant that we previously proposed as a conditional-live HIV-1 vaccine. With dox, this virus spreads efficiently to all HIV-susceptible cells. Subsequent dox withdrawal generates cells with a transcriptionally silent integrated provirus, but with an active shRNA expression cassette. Because the shRNA targets viral sequences that are removed from the vector construct, there is no self-targeting, yet there is specific shutdown of HIV-1 replication.
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Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
HIV-1
/
RNA Interferente Pequeno
/
Interferência de RNA
/
Vetores Genéticos
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Holanda