Tat-dependent conditionally replicating adenoviruses expressing diphtheria toxin A for specifically killing HIV-1-infected cells.
Mol Ther
; 32(7): 2316-2327, 2024 Jul 03.
Article
in En
| MEDLINE
| ID: mdl-38734901
ABSTRACT
HIV-1 infection remains a public health problem with no cure. Although antiretroviral therapy (ART) is effective for suppressing HIV-1 replication, it requires lifelong drug administration due to a stable reservoir of latent proviruses and may cause serious side effects and drive the emergence of drug-resistant HIV-1 variants. Gene therapy represents an alternative approach to overcome the limitations of conventional treatments against HIV-1 infection. In this study, we constructed and investigated the antiviral effects of an HIV-1 Tat-dependent conditionally replicating adenovirus, which selectively replicates and expresses the diphtheria toxin A chain (Tat-CRAds-DTA) in HIV-1-infected cells both in vitro and in vivo. We found that Tat-CRAds-DTA could specifically induce cell death and inhibit virus replication in HIV-1-infected cells mediated by adenovirus proliferation and DTA expression. A low titer of progeny Tat-CRAds-DTA was also detected in HIV-1-infected cells. In addition, Tat-CRAds-DTA showed no apparent cytotoxicity to HIV-1-negative cells and demonstrated significant therapeutic efficacy against HIV-1 infection in a humanized mouse model. The findings in this study highlight the potential of Tat-CRAds-DTA as a new gene therapy for the treatment of HIV-1 infection.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Virus Replication
/
Genetic Therapy
/
HIV Infections
/
Adenoviridae
/
HIV-1
/
Diphtheria Toxin
/
Tat Gene Products, Human Immunodeficiency Virus
/
Genetic Vectors
Limits:
Animals
/
Humans
Language:
En
Journal:
Mol Ther
/
Mol. ther
/
Molecular therapy
Journal subject:
BIOLOGIA MOLECULAR
/
TERAPEUTICA
Year:
2024
Document type:
Article
Country of publication:
Estados Unidos