Publication: Enhanced Transduction of Macaca fascicularis Hematopoietic Cells with Chimeric Lentiviral Vectors
Issued Date
2019-10-01
Resource Type
ISSN
15577422
10430342
10430342
Other identifier(s)
2-s2.0-85072848568
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Human Gene Therapy. Vol.30, No.10 (2019), 1306-1323
Suggested Citation
Karine Sii-Felice, Javier Castillo Padilla, Francis Relouzat, Joëlle Cheuzeville, Siriporn Tantawet, Leïla Maouche, Roger Le Grand, Philippe Leboulch, Emmanuel Payen Enhanced Transduction of Macaca fascicularis Hematopoietic Cells with Chimeric Lentiviral Vectors. Human Gene Therapy. Vol.30, No.10 (2019), 1306-1323. doi:10.1089/hum.2018.179 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/50069
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Enhanced Transduction of Macaca fascicularis Hematopoietic Cells with Chimeric Lentiviral Vectors
Abstract
© 2019, Mary Ann Liebert, Inc. Recent marketing approval for genetically engineered hematopoietic stem and T cells bears witness to the substantial improvements in lentiviral vectors over the last two decades, but evaluations of the long-term efficacy and toxicity of gene and cell therapy products will, nevertheless, require further studies in nonhuman primate models. Macaca fascicularis monkeys from Mauritius have a low genetic diversity and are particularly useful for reproducible drug testing. In particular, they have a genetically homogeneous class I major histocompatibility complex system that probably mitigates the variability of the response to simian immunodeficiency virus infection. However, the transduction of simian cells with human immunodeficiency virus type 1 (HIV-1)-derived vectors is inefficient due to capsid-specific restriction factors, such as the tripartite motif-containing protein tripartite motif 5α, which prevent infection with non-host-adapted retroviruses. This study introduced the modified capsid of the macaque-trophic HIV-1 clone MN4/LSQD into the packaging system and compared transduction efficiencies between hematopoietic cells transduced with this construct and cells transduced with HIV-1 NL4-3-derived packaging constructs. Capsid modification increased transduction efficiency in all hematopoietic cells tested (by factors of up to 10), including hematopoietic progenitor cells, repopulating cells, and T cells from Mauritian Macaca fascicularis, regardless of vector structure or purification method. The study also established culture conditions similar to those used in clinical practice for the efficient transduction of hematopoietic stem and progenitor CD34+ cells. These results suggest that the procedure is suitable for use in Mauritian Macaca fascicularis, which can therefore be used as a model in preclinical studies for hematopoietic gene and cell therapy.