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The last two years in scientific news
Highlight | Scientific result | Scientific publications | Gene and cell therapy | Health ＆ life sciences
Researchers from Innovative Therapies Unit (STI/Service des Thérapies Innovantes) have developed a new generation of lentivirus, paving the way for the use of Mauritian cynomolgus macaque as a pre-clinical study model for the development of new gene therapy products.
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-containng protein tripartite motif 5α,
which prevent infection with non-hostadapted retroviruses.
from STI have developed a 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.
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.
This 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.
Enhanced Transduction of Macaca fascicularis Hematopoietic Cells
with Chimeric Lentiviral Vectors | Human Gene Therapy
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