In vivo repopulation of cytoplasmically gene transferred hematopoietic cells by temperature-sensitive mutant of recombinant Sendai viral vector

Kumi Yoshida, Yoshikazu Yonemitsu, Sakura Tanaka, Shuro Yoshida, Satoko Shibata, Haruhiko Kondo, Shinji Okano, Fumihiko Ishikawa, Koichi Akashi, Makoto Inoue, Mamoru Hasegawa, Katsuo Sueishi

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)811-816
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume361
Issue number3
DOIs
Publication statusPublished - Sep 28 2007

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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