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Novel Cell and Gene Therapies for HIV
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DOI：10.1101/cshperspect.a007179.png)
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Abstract
En 中文
Highly active antiretroviral therapy dramatically improves survival in HIV-infected patients. However, persistence of HIV in reservoirs has necessitated lifelong treatment that can be complicated by cumulative toxicities, incomplete immune restoration, and the emergence of drug-resistant escape mutants. Cell and gene therapies offer the promise of preventing progressive HIV infection by interfering with HIV replication in the absence of chronic antiviral therapy. Individuals homozygous for a deletion in the CCR5 gene (CCR5 Delta 32) are largely resistant to infection from R5-topic HIV-1 strains, which are most commonly transmitted. A recent report that an HIV-infected patient with relapsed acute myelogenous leukemia was effectively cured from HIV infection after transplantation of hematopoietic stem/progenitor cells (HSC) from a CCR5D32 homozygous donor has generated renewed interest in developing treatment strategies that target viral reservoirs and generate HIV resistance in a patient's own cells. Although the development of cell-based and gene transfer therapies has been slow, progress in a number of areas is evident. Advances in the fields of gene-targeting strategies, T-cell-based approaches, and HSCs have been encouraging, and a series of ongoing and planned trials to establish proof of concept for strategies that could lead to successful cell and gene therapies for HIV are under way. The eventual goal of these studies is to eliminate latent viral reservoirs and the need for lifelong antiretroviral therapy.
Keywords:
IMMUNODEFICIENCY-VIRUS TYPE-1
BONE-MARROW-TRANSPLANTATION
HEMATOPOIETIC STEM-CELLS
CHEMOKINE RECEPTOR 5
HUMAN T-CELLS
ZINC-FINGER NUCLEASES
SHORT HAIRPIN RNA
ANTIRETROVIRAL THERAPY
PROGENITOR CELLS
HEMATOLOGIC MALIGNANCIES
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