Polysaccharide-oligoamine based conjugates for gene delivery.
This work describes a versatile and universal polycation system based on oligoamines grafted on natural polysaccharides that is capable of complexing various plasmids and administering them into various cells in high yield to produce a desired protein. These polycations are expected to better meet the requirements for effective complexation and delivery of plasmid or an antisense and to biodegrade into nontoxic components at a controlled rate. The developed biodegradable polycations are based on spermine, a natural tetramine, conjugated to dextran or arabinogalactan. These polycations were prepared by reductive amination of oxidized polysaccharides with the desired oligoamines. The Schiff base conjugates thus obtained were reduced to the stable amine conjugates by sodium borohydride. Over 300 different polycations were prepared starting from various polysaccharides and oligoamines, mainly oligoamines of two to four amino groups. Although most of these conjugates formed stable complexes with various plasmids as determined by turbidity experiments, only a few polycations were found to be active in transfecting cells. This work indicates that the structure of the polycation plays a significant role in the transfection activity of polycations.
Azzam
Tony
T
Department of Medicinal Chemistry and Natural Products, School of Pharmacy, Faculty of Medicine, The Hebrew University, Jerusalem 91120, Israel.
Eliyahu
Hagit
H
Shapira
Libi
L
Linial
Michal
M
Barenholz
Yechezkel
Y
Domb
Abraham J
AJ
D002412:Cations; D002460:Cell Line; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D019382:Human Growth Hormone / Q000235:genetics; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics; D008856:Microscopy, Fluorescence; D008970:Molecular Weight; D010957:Plasmids; D011073:Polyamines / Q000737:chemistry*; D011134:Polysaccharides / Q000737:chemistry*; D014162:Transfection
D002412:Cations; D008164:Luminescent Proteins; D011073:Polyamines; D011134:Polysaccharides; D019382:Human Growth Hormone; D049452:Green Fluorescent Proteins; D008156:Luciferases