TY - JOUR
T1 - Design of imidazole-containing endosomolytic biopolymers for gene delivery
AU - Pack, Daniel W.
AU - Putnam, David
AU - Langer, Robert
PY - 2000/1/20
Y1 - 2000/1/20
N2 - The development of safe and effective gene delivery agents poses a great challenge in the quest to make human gene therapy a reality. Cationic polymers represent one important class of materials for gene delivery, but to date they have shown only moderate efficiency. Improving the efficiency will require the design of new polymers incorporating optimized gene delivery properties. For example, inefficient release of the DNA/polymer complex from endocytic vesicles into the cytoplasm is one of the primary causes of poor gene delivery. Here we report the synthesis of a biocompatible, imidazole- containing polymer designed to overcome this obstacle. DNA/polymer polyplexes incorporating this polymer were shown to have desirable physico-chemical properties for gene delivery and are essentially nontoxic. Using this system, mammalian cells in vitro were transfected in the absence of any exogenous endosomolytic agent such as chloroquine.
AB - The development of safe and effective gene delivery agents poses a great challenge in the quest to make human gene therapy a reality. Cationic polymers represent one important class of materials for gene delivery, but to date they have shown only moderate efficiency. Improving the efficiency will require the design of new polymers incorporating optimized gene delivery properties. For example, inefficient release of the DNA/polymer complex from endocytic vesicles into the cytoplasm is one of the primary causes of poor gene delivery. Here we report the synthesis of a biocompatible, imidazole- containing polymer designed to overcome this obstacle. DNA/polymer polyplexes incorporating this polymer were shown to have desirable physico-chemical properties for gene delivery and are essentially nontoxic. Using this system, mammalian cells in vitro were transfected in the absence of any exogenous endosomolytic agent such as chloroquine.
KW - Chloroquine
KW - Endosomolytic polymer
KW - Gene delivery
KW - Polycations
KW - Polyhistidine
KW - Polyplexes
UR - http://www.scopus.com/inward/record.url?scp=0034688198&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034688198&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1097-0290(20000120)67:2<217::AID-BIT11>3.0.CO;2-Q
DO - 10.1002/(SICI)1097-0290(20000120)67:2<217::AID-BIT11>3.0.CO;2-Q
M3 - Article
C2 - 10592519
AN - SCOPUS:0034688198
SN - 0006-3592
VL - 67
SP - 217
EP - 223
JO - Biotechnology and Bioengineering
JF - Biotechnology and Bioengineering
IS - 2
ER -