Retronectin enhances lentivirus-mediated gene delivery into hematopoietic progenitor cells.
Genetic modification of hematopoietic stem cells holds great promise in the treatment of hematopoietic disorders. However, clinical application of gene delivery has been limited, in part, by low gene transfer efficiency. To overcome this problem, we investigated the effect of retronectin (RN) on lentiviral-mediated gene delivery into hematopoietic progenitor cells (HPCs) derived from bone marrow both in vitro and in vivo. RN has been shown to enhance transduction by promoting colocalization of lentivirus and target cells. We found that RN enhanced lentiviral transfer of the VENUS transgene into cultured c-Kit(+) Lin(-) HPCs. As a complementary approach, in vivo gene delivery was performed by subjecting mice to intra-bone marrow injection of lentivirus or a mixture of RN and lentivirus. We found that co-injection with RN increased the number of VENUS-expressing c-Kit(+) Lin(-) HPCs in bone marrow by 2-fold. Further analysis of VENUS expression in colony-forming cells from the bone marrow of these animals revealed that RN increased gene delivery among these cells by 4-fold. In conclusion, RN is effective in enhancing lentivirus-mediated gene delivery into HPCs.
Lee
Hyun-Joo
HJ
Graduate School of Life Science and Biotechnology, Pochon CHA University, CHA Stem Cell Institute, 605 Yeoksam 1-dong, Kangnam-gu, Seoul 135-081, Republic of Korea.
Lee
Yong-Soo
YS
Kim
Hye-Sun
HS
Kim
Yu-Kyung
YK
Kim
Jae-Hwan
JH
Jeon
Seong-Ho
SH
Lee
Hyeon-Woo
HW
Kim
Sinae
S
Miyoshi
Hiroyuki
H
Chung
Hyung-Min
HM
Kim
Dong-Ku
DK
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D005353:Fibronectins / Q000737:chemistry / Q000494:pharmacology*; D018014:Gene Transfer Techniques; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D039902:Multipotent Stem Cells / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000494:pharmacology*; D015854:Up-Regulation
D005353:Fibronectins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C545354:retronectin