Cell-Delivered Entry Inhibitors for HIV-1: CCR5 Downregulation and Blocking Virus/Membrane Fusion in Defending the Host Cell Population.
AIDS Patient Care STDS
; 30(12): 545-550, 2016 12.
Article
en En
| MEDLINE
| ID: mdl-27905841
ABSTRACT
HIV-1 infection requires the presence of the CD4 receptor on the target cell surface and a coreceptor, predominantly CC-chemokine receptor 5 (CCR5). It has been shown that individuals who are homozygous for a defective CCR5 gene are protected from HIV-1 infection. A novel self-inactivating lentiviral vector LVsh5/C46 (Cal-1) has been engineered to block HIV-1 infection with two viral entry inhibitors, conferring resistance to HIV-1 infection from both CCR5 and CXCR4 tropic strains. Cal-1 encodes a short hairpin RNA (sh5) to downregulate CCR5 and C46, an HIV-1 fusion inhibitor. Gene therapy by Cal-1 is aimed at transducing CD4+ T cells and CD34+ hematopoietic stem/progenitor cells in an autologous transplant setting. Pre-clinical safety and efficacy studies in vitro and in vivo (humanized mouse model and nonhuman primates) have shown that Cal-1 is safe with no indication of any toxicity risk and acts to decrease viral load and increase CD4 counts. Two clinical trials are underway using Cal-1 a phase I/II study to assess safety and feasibility in an adult HIV-1-positive population not on antiretroviral therapy (ART); and a second Fred Hutchinson Investigator Initiated phase I study to assess safety and feasibility in adults with HIV-1-associated non-Hodgkin or Hodgkin lymphoma.
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Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
Problema de salud:
2_enfermedades_transmissibles
Asunto principal:
Proteínas Recombinantes de Fusión
/
Terapia Genética
/
Infecciones por VIH
/
Receptores del VIH
/
VIH-1
/
Receptores CCR5
/
Fusión de Membrana
Límite:
Adult
/
Animals
/
Humans
Idioma:
En
Revista:
AIDS Patient Care STDS
Asunto de la revista:
DOENCAS SEXUALMENTE TRANSMISSIVEIS
/
SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS)
Año:
2016
Tipo del documento:
Article