In vivo repopulation of cytoplasmically gene transferred hematopoietic cells by temperature-sensitive mutant of recombinant Sendai viral vector.
Recent clinical studies revealed 'proof of concept' of gene therapy targeting hematopoietic stem cells (HSCs) to treat hematopoietic disorders. However, vector integration-related adverse events of retroviral vectors have slowed progress in this field. As an initial step to overcoming this hurdle, we examined the potential of an improved cytoplasmic RNA vector, temperature-sensitive mutant non-transmissible recombinant Sendai virus (ts-rSeV/dF), for gene transfer to murine HSCs and progenitors. Both conventional vector and ts-rSeV/dF-GFP showed efficient gene transfer to T-lymphocyte-depleted syngeneic bone marrow cells (BMCs) (>85%), but only BMCs treated with ts-rSeV/dF-GFP but not with conventional vector efficiently repopulated in the recipient mice, associated with multilineage differentiation in vitro and in vivo. To our knowledge, this is the first demonstration of the in vivo reconstruction of hematopoietic series by cytoplasmically gene transferred BMCs, that warrants further investigation to realize this strategy in clinical settings.
Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Kumi
K
Yoshida
Yoshikazu
Y
Yonemitsu
Sakura
S
Tanaka
Shuro
S
Yoshida
Satoko
S
Shibata
Haruhiko
H
Kondo
Shinji
S
Okano
Fumihiko
F
Ishikawa
Koichi
K
Akashi
Makoto
M
Inoue
Mamoru
M
Hasegawa
Katsuo
K
Sueishi
D000818:Animals; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D019070:Cell Lineage; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D029082:Sendai virus / Q000235:genetics*; D013696:Temperature; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism
D014759:Viral Envelope Proteins