Affiliation:
1. Department of Microbiology and Molecular Genetics, New Jersey Medical School, Rutgers University, 225 Warren Street, Newark, NJ 070101, USA
2. Department of Pain Medicine and Shenzhen Municipal Key Laboratory for Pain Medicine, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen 518060, China
3. Department of Microbiology, Howard University College of Medicine, 520 W Street NW, Washington, DC 20059, USA
Abstract
Viral vectors have emerged as powerful tools for delivering and expressing foreign genes, playing a pivotal role in gene therapy. Among these vectors, cytomegalovirus (CMV) stands out as a promising viral vector due to its distinctive attributes including large packaging capacity, ability to achieve superinfection, broad host range, capacity to induce CD8+ T cell responses, lack of integration into the host genome, and other qualities that make it an appealing vector candidate. Engineered attenuated CMV strains such as Towne and AD169 that have a ~15 kb genomic DNA deletion caused by virus passage guarantee human safety. CMV’s large genome enables the efficient incorporation of substantial foreign genes as demonstrated by CMV vector-based therapies for SIV, tuberculosis, cancer, malaria, aging, COVID-19, and more. CMV is capable of reinfecting hosts regardless of prior infection or immunity, making it highly suitable for multiple vector administrations. In addition to its broad cellular tropism and sustained high-level gene expression, CMV triggers robust, virus-specific CD8+ T cell responses, offering a significant advantage as a vaccine vector. To date, successful development and testing of murine CMV (MCMV) and rhesus CMV (RhCMV) vectors in animal models have demonstrated the efficacy of CMV-based vectors. These investigations have explored the potential of CMV vectors for vaccines against HIV, cancer, tuberculosis, malaria, and other infectious pathogens, as well as for other gene therapy applications. Moreover, the generation of single-cycle replication CMV vectors, produced by deleting essential genes, ensures robust safety in an immunocompromised population. The results of these studies emphasize CMV’s effectiveness as a gene delivery vehicle and shed light on the future applications of a CMV vector. While challenges such as production complexities and storage limitations need to be addressed, ongoing efforts to bridge the gap between animal models and human translation continue to fuel the optimism surrounding CMV-based vectors. This review will outline the properties of CMV vectors and discuss their future applications as well as possible limitations.
Funder
National Institute on Minority Health and Health Disparities of the National Institutes of Health
Science and Technology Major Project of Shenzhen Nanshan District Health System
Subject
Virology,Infectious Diseases
Reference123 articles.
1. Simple and highly efficient BAC recombineering using galK selection;Warming;Nucleic Acids Res.,2005
2. Tang, Q., Silver, B.S., and Zhu, H. (2012). In Protocol of a Seamless Recombination with Specific Selection Cassette in PCR-Based Site-Directed Mutagenesis. Appl. Biol.
3. Gbedande, K., Ibitokou, S.A., Ong, M.L., Degli-Esposti, M.A., Brown, M.G., and Stephens, R. Boosting Live Malaria Vaccine with Cytomegalovirus Vector Can Prolong Immunity through Innate and Adaptive Mechanisms. bioRxiv.
4. Vaccine vectors: The bright side of cytomegalovirus;Mendez;Med. Microbiol. Immunol.,2019
5. A novel murine cytomegalovirus vaccine vector protects against Mycobacterium tuberculosis;Beverley;J. Immunol.,2014
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献