Integrase deficient lentiviral vector: prospects for safe clinical applications

PeerJ. 2022 Aug 12:10:e13704. doi: 10.7717/peerj.13704. eCollection 2022.

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.

Keywords: Cell Reprogramming; Cell death; Gene therapy; Immunization; Integrase-deficient lentiviral vector.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genetic Vectors / genetics
  • Genome
  • HIV-1* / genetics
  • Integrases* / genetics
  • Transgenes

Substances

  • Integrases

Grants and funding

The study was supported by the Ministry of Higher Education Malaysia (MOHE) for the awarded grant FRGS/1/2020/SKK06/UKM/03/4 and Universiti Kebangsaan Malaysia through the Faculty of Medicine grant (FF-2020-327). This funding body accepted the study as proposed. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.