Humanization of Laboratory Mice for HIV Research: Current Methods and Perspectives

Relevance of the Topic Studying the pathogenesis of HIV infection and developing novel therapeutic strategies require adequate pre­clinical models that replicate key aspects of viral interaction with the human immune system. Traditional mod­els, such as primates or transgenic animals, face significant limitations, including high costs, ethical concerns, and insufficient accuracy in mimicking human immune responses (Dash PK et al., 2021, Bennett MS, Akkina R, 2013). In this context, humanized mice, created by transplanting human hematopoietic stem cells (HSCs) or tis­sues into immunodeficient mice, have emerged as revolutionary tools. These models enable the study of HIV infection in vivo, including latent reservoirs, immune responses, and the efficacy of antiretroviral therapy (ART) (Zhang C et al., 2023, Baroncini L et al., 2023). Article Objective This review aims to systematize modern methods of humanizing mice, evaluate their applications in HIV re­search, and highlight key challenges and future prospects. Special emphasis is placed on the role of CRISPR-Cas systems in editing genes such as CCR5 and their contribution to developing functional cure strategies (Rotheme­jer FH, et al., 2023, Khamaikawin W, et al.. 2024). Summary of Sections The article is divided into four main chapters. The first chapter examines contemporary humanization methods, including immunodeficient mouse strains (e.g., NOD/SCID/γc<sup>null</sup> and Rag2<sup>null</ sup>γc<sup>null</sup>) and HSC transplantation. The second chapter analyzes the use of these models in HIV research, from evaluating latent reservoirs to testing gene therapies. The third chapter addresses challenges such as incomplete immune system reconstruction and long-term study limitations, alongside prospects like CRISPR-Cas integration and improved humanization techniques. The concluding section underscores the importance of further re­search to overcome existing barriers. Article Structure This review follows a classical scientific structure, progressing from general context to technical and applied aspects. Each chapter includes critical analysis of sources and references to key studies, ensuring an evidence-based foundation for all claims. Literature Search Strategy This review synthesizes data from peer-reviewed articles, clinical studies, and preclinical reports indexed in PubMed, Web of Science, and Scopus between 2010 and 2024. The search utilized the following keywords and their combinations: “humanized mice”, “HIV latency”, “CRISPR-Cas”, “CCR5 editing”, and “antiretroviral therapy”. Inclusion criteria priori­tized studies that directly compared humanization methods (e.g., CD34<sup>+</sup> vs. BLT models), evaluated CRISPR-based interventions in HIV-infected humanized mice, and addressed ethical or technical challenges in model optimization. Exclus