Genetic therapies against HIV.

Area of Science:

• Biotechnology
• Virology
• Immunology

Background:

• Highly active antiretroviral therapy (HAART) prolongs life for individuals with HIV but requires lifelong treatment and can lead to toxicities and drug resistance.
• Gene therapy presents a promising alternative to HAART by aiming for sustained interference with HIV replication, potentially eliminating the need for chronic chemotherapy.

Purpose of the Study:

• To explore and summarize current gene-targeting strategies for preventing progressive HIV infection.
• To review advancements in T-cell-based and stem cell-based gene therapies for HIV.
• To discuss methods for overcoming viral resistance in gene therapy approaches.

Main Methods:

• Development of RNA-based gene-targeting agents (ribozymes, antisense, RNA aptamers, small interfering RNA).
• Utilizing protein-based agents (mutant HIV Rev protein M10, fusion inhibitors, zinc-finger nucleases).
• Advancing T-cell-based strategies (gene-modified HIV-resistant T cells, lentiviral gene delivery, CD8(+) T cells, T bodies, engineered T-cell receptors) and hematopoietic stem cell therapies.

Main Results:

• Various gene-targeting strategies are under development, showing potential for sustained interference with HIV replication.
• T-cell and stem cell-based therapies are emerging as viable options to confer HIV resistance.
• Combinatorial genetic approaches targeting both viral and host factors are being investigated to combat viral resistance.

Conclusions:

• Gene therapy holds significant promise for a functional cure or long-term remission of HIV infection.
• Ongoing and planned clinical trials are evaluating the efficacy and safety of these novel gene-targeting strategies.
• Future HIV treatment may involve gene-based interventions to achieve durable viral suppression without chronic drug regimens.