Infectious Disease Mouse Models (HIV, HBV)

Infectious disease mouse models for studying HIV, HBV and other infectious diseases are available from TransCure bioServices.

The CD34+ Humanized Mice, a promising player in the preclinical HIV research arena

CD34+ Humanized Mice have already demonstrated their value in HIV research. They have been used to model key aspects of HIV infection, including viral replication, CD4+ T cell depletion, immune response, and latency. They’ve also been instrumental in testing the efficacy of antiretroviral drugs and potential HIV vaccines.

Infectious Disease Mouse Models HIV HBV

Make sure to check out our complimentary webinar “How Humanized Mice Studies Can Accelerate Preclinical Research in Infectious Diseases“, a 2 minute introduction is provided here.

WEBINAR: How Humanized Mice Studies Can Accelerate Preclinical Research in Infectious Diseases

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The following case studies illustrate the significant contributions of TransCure bioServices Humanized mice in advancing HIV preclinical research. Using CD34+ humanized mice, researchers are now able to accelerate the development and testing of potential therapeutics, emphasizing the importance of these models in the fight against HIV.

Case Study #1: The Development of a long-acting antiviral agent

In this study published by ViiV HealthCare, BMS and TransCure bioServices, Wensel et al., have made significant strides towards developing a long-acting antiretroviral agent, GSK3732394. This biologic offers a potential alternative to daily oral therapy, a critical concern for HIV-1-infected individuals due to the life-long burden, stigma, and risk of developing drug-resistant viral variants. GSK3732394 has shown to be highly effective in a humanized mouse model of infection and is currently undergoing clinical trials.

Case Study #2: GS-CA1, A New Small-Molecule HIV Capsid Inhibitor

One of the breakthroughs in HIV preclinical research using CD34+ humanized mice involved the development of GS-CA1, an HIV capsid inhibitor. In this study, Gilead scientists have demonstrated that the small molecule exhibits impressive potency against all major HIV-1 types and HIV-2, including drug-resistant variants. GS-CA1 was shown to have high antiviral efficacy as a long-acting injectable monotherapy in a humanized mouse model of HIV-1 infection provided by TransCure bioServices, outperforming other existing long-acting agents.

Case Study #3: Targeting the HIV reservoir using Venetoclax as a BCL-2 inhibitor

BCL-2, a prosurvival protein, is believed to contribute to HIV persistence. Therefore, targeting this protein could potentially facilitate HIV eradication. In a study performed by the Mayo Clinic using CD34+ humanized mice, the BCL-2 inhibitor venetoclax was found to significantly decrease plasma viremia, normalize CD4:CD8 ratios, and result in more mice with undetectable provirus levels than the control.

LET’S TALK

References:

Wensel D, Sun Y, Davis J, Li Z, Zhang S, McDonagh T, Langley D, Mitchell T, Tabruyn S, Nef P, Cockett M, Krystal M. GSK3732394: a Multi-specific Inhibitor of HIV Entry. J Virol. 2019 Sep 30;93(20):e00907-19. doi: 10.1128/JVI.00907-19. PMID: 31375580; PMCID: PMC6798092.

Yant SR, Mulato A, Hansen D, Tse WC, Niedziela-Majka A, Zhang JR, Stepan GJ, Jin D, Wong MH, Perreira JM, Singer E, Papalia GA, Hu EY, Zheng J, Lu B, Schroeder SD, Chou K, Ahmadyar S, Liclican A, Yu H, Novikov N, Paoli E, Gonik D, Ram RR, Hung M, McDougall WM, Brass AL, Sundquist WI, Cihlar T, Link JO. A highly potent long-acting small-molecule HIV-1 capsid inhibitor with efficacy in a humanized mouse model. Nat Med. 2019 Sep;25(9):1377-1384. doi: 10.1038/s41591-019-0560-x. Epub 2019 Sep 9. PMID: 31501601; PMCID: PMC7396128.

Chandrasekar AP, Cummins NW, Natesampillai S, Misra A, Alto A, Laird G, Badley AD. The BCL-2 Inhibitor Venetoclax Augments Immune Effector Function Mediated by Fas Ligand, TRAIL, and Perforin/Granzyme B, Resulting in Reduced Plasma Viremia and Decreased HIV Reservoir Size during Acute HIV Infection in a Humanized Mouse Model. J Virol. 2022 Dec 21;96(24):e0173022. doi: 10.1128/jvi.01730-22. Epub 2022 Nov 30. PMID: 36448802; PMCID: PMC9769373.