Non-integrating Lentiviral vectors in clinical applications: A glance through
Document Type
Article
Publication Date
1-1-2022
Abstract
Lentiviral vectors (LVs) play an important role in gene therapy and have proven successful in clinical trials. LVs are capable of integrating specific genetic materials into the target cells and allow for long-term expression of the cDNA of interest. The use of non-integrating LVs (NILVs) reduces insertional mutagenesis and the risk of malignant cell transformation over integrating lentiviral vectors. NILVs enable transient expression or sustained episomal expression, especially in non-dividing cells. Important modifications have been made to the basic human immunodeficiency virus (HIV) structures to improve the safety and efficacy of LVs. NILV-aided transient expression has led to more pre-clinical studies on primary immunodeficiencies, cytotoxic cancer therapies, and hemoglobinopathies. Recently, the third generation of self-inactivating LVs was applied in clinical trials for recombinant protein production, vaccines, gene therapy, cell imaging, and induced pluripotent stem cell (iPSC) generation. This review discusses the basic lentiviral biology and the four systems used for generating NILV designs. Mutations or modifications in LVs and their safety are addressed with reference to pre-clinical studies. The detailed application of NILVs in promising pre-clinical studies is also discussed.
Keywords
HIV, Integrate-deficient, Lentiviral-vector, Clinical application, Vaccinations, NILV
Divisions
fac_eng
Funders
Ministry of Education, Malaysia[FRGS/1/2020/SKK06/UKM/03/4],Universiti Kebangsaan Malaysia[FF-2020-327],Universiti Kebangsaan Malaysia[UKM PPI/111/8/JEP-2021-347]
Publication Title
Biomedicines
Volume
10
Issue
1
Publisher
MDPI
Publisher Location
ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND