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Table 3 Gene therapeutic strategies used to control HIV-1 infection in the new generation of humanized mice

From: The utility of the new generation of humanized mice to study HIV-1 infection: transmission, prevention, pathogenesis, and treatment

Humanized mouse model Strategy Findings Reference
RAG-hu mice Lentiviral vector transduction of HSCs with anti-nef shRNA construct Lentivirally-transduced HSCs can engraft in RAG-hu mice. Ex vivo challenge with HIV-1 showed preferential protection of transduced cells. [60]
hNOG mice Lentiviral vector transduction of HSCs with gene encoding neutralizing human antibody to HIV-1 (2G12) Lentivirally-transduced HSCs can engraft in hNOG mice. Antibody was produced; viremia was ~70-fold reduced and number of infected splenocytes was reduced ~200-fold. [68]
hNOG mice Disrupt CCR5 gene in HSCs by zinc finger nucleases ~17% of all alleles in the HSC population were gene modified; engraftment was still successful. Gene-modified cells were positively selected during HIV-1 infection. [74]
BLT mice Targeted delivery of an anti-CCR5 siRNA to human lymphocytes in vivo CCR5 expression was silenced and plasma viral load was decreased ~30-fold relative to controls. No CD4 T cell depletion noted through 55 days. [81]
BLT mice Lentiviral transduction of HSCs with anti-CCR5 shRNA construct CCR5 expression was silenced in a variety of cell types and tissue sites. Protection against infection was measured ex vivo. [79]
RAG-hu mice RNA-based aptamers used to neutralize virus and/or to deliver anti-tat/rev siRNA to infected cells Viral load decreased relative to controls; helper T cell depletion blocked. Combination therapy more effective than aptamer alone. [54]
hNOG mice Targeting of siRNAs to block expression of CD4, CCR5, or viral RNAs to mature human T cells Viral load was lower after treatment, despite a moderate and transient effect on receptor knockdown. CD4 T cell levels preserved. [69]
hNOG mice Lentiviral vector transduction of HSCs to express antisense RNA to env Only a low percentage of cells were transduced (4-11%); no effect on viral load; virus mutated targeted env sequences. [70]
hNOG mice Lentiviral transduction of mature CD4 T cells to produce viral entry inhibitor Transduced cells expressing entry inhibitor expanded relative to non-transduced or control transduced cells, indicating protection. [125]