PMID- 9349433 OWN - NLM STAT- MEDLINE DCOM- 19971120 LR - 20131121 IS - 0969-7128 (Print) IS - 0969-7128 (Linking) VI - 4 IP - 9 DP - 1997 Sep TI - Protamine sulfate enhances lipid-mediated gene transfer. PG - 961-8 AB - A polycationic peptide, protamine sulfate, USP, has been shown to be able to condense plasmid DNA efficiently for delivery into several different types of cells in vitro by several different types of cationic liposomes. The monovalent cationic liposomal formulations (DC-Chol and lipofectin) exhibited increased transfection activities comparable to that seen with the multivalent cationic liposome formulation, lipofectamine. This suggests that lipofectamine's superior in vitro activity arises from its ability to condense DNA efficiently and that protamine's primary role is that of a condensation agent, although it also possesses several amino acid sequences resembling that of a nuclear localization signal. While the use of polycations to condense DNA has been previously reported, the of protamine sulfate, USP as a condensation agent was found to be superior to poly-L-lysine as well as to various other types of protamine. These differences among various salt forms of protamine appear to be attributable to structural differences between the protamines and not due to differences in the net charge of the molecule. The appearance of lysine residues within the protamine molecule correlate with a reduction in binding affinity to plasmid DNA as well as an observed loss in transfection enhancing activity. This finding sheds light on the structural requirements of condensation agents for use in gene transfer protocols. Furthermore, protamine sulfate, USP is an FDA-approved compound with a documented safety profile and could be readily used as an adjuvant to a human gene therapy protocol. FAU - Sorgi, F L AU - Sorgi FL AD - Department of Pharmacology, University of Pittsburgh School of Medicine, PA 15261, USA. FAU - Bhattacharya, S AU - Bhattacharya S FAU - Huang, L AU - Huang L LA - eng GR - CA 59327/CA/NCI NIH HHS/United States GR - CA 64654/CA/NCI NIH HHS/United States GR - CA 71731/CA/NCI NIH HHS/United States GR - etc. PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Gene Ther JT - Gene therapy JID - 9421525 RN - 0 (Cation Exchange Resins) RN - 0 (Cations) RN - 0 (Lipids) RN - 0 (Lipofectamine) RN - 0 (Liposomes) RN - 0 (Phosphatidylethanolamines) RN - 0 (Protamines) RN - 137056-72-5 (3-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol) RN - 76391-83-8 (1,2-dielaidoylphosphatidylethanolamine) RN - 97C5T2UQ7J (Cholesterol) RN - EC 1.13.12.- (Luciferases) SB - IM MH - Amino Acid Sequence MH - Animals MH - CHO Cells MH - Cation Exchange Resins MH - Cations MH - Cell Line MH - Cholesterol/analogs & derivatives MH - Cricetinae MH - Genetic Therapy/*methods MH - Humans MH - Lipids MH - Liposomes MH - Luciferases/genetics MH - Molecular Sequence Data MH - Phosphatidylethanolamines MH - *Protamines/genetics MH - *Transfection EDAT- 1998/02/12 00:00 MHDA- 1998/02/12 00:01 CRDT- 1998/02/12 00:00 PHST- 1998/02/12 00:00 [pubmed] PHST- 1998/02/12 00:01 [medline] PHST- 1998/02/12 00:00 [entrez] AID - 10.1038/sj.gt.3300484 [doi] PST - ppublish SO - Gene Ther. 1997 Sep;4(9):961-8. doi: 10.1038/sj.gt.3300484.