Integrase deficient lentiviral vector: prospects for safe clinical applications

Author:

Yew Chee-Hong Takahiro1,Gurumoorthy Narmatha1,Nordin Fazlina1,Tye Gee Jun2,Wan Kamarul Zaman Wan Safwani3,Tan Jun Jie4,Ng Min Hwei1

Affiliation:

1. Centre for Tissue Engineering and Regenerative Medicine (CTERM), Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Kuala Lumpur, Malaysia

2. Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Pulau Pinang, Malaysia

3. Department of Biomedical Engineering, Faculty of Engineering, University Malaya (UM), Kuala Lumpur, Malaysia

4. Advanced Medical and Dental Institute, Universiti Sains Malaysia (USM), Bertam, Kepala Batas, Pulau Pinang, Malaysia

Abstract

HIV-1 derived lentiviral vector is an efficient transporter for delivering desired genetic materials into the targeted cells among many viral vectors. Genetic material transduced by lentiviral vector is integrated into the cell genome to introduce new functions, repair defective cell metabolism, and stimulate certain cell functions. Various measures have been administered in different generations of lentiviral vector systems to reduce the vector’s replicating capabilities. Despite numerous demonstrations of an excellent safety profile of integrative lentiviral vectors, the precautionary approach has prompted the development of integrase-deficient versions of these vectors. The generation of integrase-deficient lentiviral vectors by abrogating integrase activity in lentiviral vector systems reduces the rate of transgenes integration into host genomes. With this feature, the integrase-deficient lentiviral vector is advantageous for therapeutic implementation and widens its clinical applications. This short review delineates the biology of HIV-1-erived lentiviral vector, generation of integrase-deficient lentiviral vector, recent studies involving integrase-deficient lentiviral vectors, limitations, and prospects for neoteric clinical use.

Funder

Ministry of Higher Education Malaysia

Universiti Kebangsaan Malaysia through the Faculty of Medicine grant

Publisher

PeerJ

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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