Cell and Gene Therapy for HIV Cure

Abstract

As the HIV pandemic rapidly spread worldwide in the 1980s and 1990s, a new approach to treat cancer, genetic diseases, and infectious diseases was also emerging. Cell and gene therapy strategies are connected with human pathologies at a fundamental level, by delivering DNA and RNA molecules that could correct and/or ameliorate the underlying genetic factors of any illness. The history of HIV gene therapy is especially intriguing, in that the virus that was targeted was soon co-opted to become part of the targeting strategy. Today, HIV-based lentiviral vectors, along with many other gene delivery strategies, have been used to evaluate HIV cure approaches in cell culture, small and large animal models, and in patients. Here, we trace HIV cell and gene therapy from the earliest clinical trials, using genetically unmodified cell products from the patient or from matched donors, through current state-of-the-art strategies. These include engineering HIV-specific immunity in T-cells, gene editing approaches to render all blood cells in the body HIV-resistant, and most importantly, combination therapies that draw from both of these respective "offensive" and "defensive" approaches. It is widely agreed upon that combinatorial approaches are the most promising route to functional cure/remission of HIV infection. This chapter outlines cell and gene therapy strategies that are poised to play an essential role in eradicating HIV-infected cells in vivo.

Clinical pharmacology in HIV cure research – what impact have we seen?

“…Nevertheless, this case was not further reproduced; a recent work by Colonna et al in cART-suppressed non-human primates infected by SIV showed how allopoietic hematopoietic cell transplantation is insufficient for HIV eradication despite high-level donor chimerism and graft versus host disease due to the persistence of HIV in multiple sites including the brain [123]. Nowadays, several strategies based on gene and cell therapy have been tested in order to evaluate HIV cure approaches from in vitro studies to clinical trial [124]. These include engineering HIV-specific immunity in T-cells, gene editing approaches to render all blood cells in the body HIV-resistant starting from the proof of concept of the "Berlin patient", and a combination of both these strategies.…”

Bringing Gene Therapies for HIV Disease to Resource-Limited Parts of the World

“…To introduce such modifications in vivo, it will be necessary to design vectors that can carry the appropriate editing systems to selected target cells after percutaneous (e.g., intravenous or intramuscular) administration. Active work in this area [55][56][57] has already highlighted the capabilities of viral (e.g., AAV and lentiviral) vectors as well as ligand-directed lipid nanoparticles, ribonucleoprotein complexes, synthetic nucleocapsids, and exosomes; given commercial opportunities in areas like oncology, it is inevitable that even more options will surface in the future.…”

Surface-Engineered Lentiviral Vectors for Selective Gene Transfer into Subtypes of Lymphocytes

“…Finally, a lot of effort is currently put into gene therapy concepts targeting HIV-infected cells. 24 , 25 Here, T cells have been modified to express antisense transcripts in an attempt to confer protection from HIV infection. 26 Similarly, the modification of T cells with membrane-anchored peptides inhibiting cell-virus fusion as well as TCRs recognizing viral antigens has been explored as a treatment option for HIV patients resistant to antiretroviral therapy.…”