title: Retronectin enhances lentivirus-mediated gene delivery into hematopoietic progenitor cells.
abstract: 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.
authors.affiliation: 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.
authors.forename: Hyun-Joo
authors.initials: HJ
authors.lastname: Lee
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Lee
authors.forename: Hye-Sun
authors.initials: HS
authors.lastname: Kim
authors.forename: Yu-Kyung
authors.initials: YK
authors.lastname: Kim
authors.forename: Jae-Hwan
authors.initials: JH
authors.lastname: Kim
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Jeon
authors.forename: Hyeon-Woo
authors.initials: HW
authors.lastname: Lee
authors.forename: Sinae
authors.initials: S
authors.lastname: Kim
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Miyoshi
authors.forename: Hyung-Min
authors.initials: HM
authors.lastname: Chung
authors.forename: Dong-Ku
authors.initials: DK
authors.lastname: Kim
mesh_terms: 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
chemical_list: D005353:Fibronectins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C545354:retronectin