Synthesis and application of a non-viral gene delivery system for immunogene therapy of cancer.
The synthesis and gene delivery application of a novel lipopolymer, PEG-PEI-CHOL (PPC), is described. PPC is composed of a low molecular weight branched polyethylenimine (PEI) covalently linked with functional groups methoxypolyethyleneglycol (PEG) and cholesterol (CHOL). The potential utility of PPC as a gene delivery polymer was evaluated by showing its ability to form stable nanocomplexes with DNA, protect DNA from degradation by DNase and mediate gene transfer in vitro and in vivo in solid tumors. The ratio of PEG/PEI/CHOL and nitrogen to phosphate (Polymer/DNA) was optimized for physico-chemical properties and gene delivery efficiency of PPC/DNA complexes. The gene therapy application of the polymer was shown following administration of a murine IL-12 plasmid (pmIL-12) formulated with PPC into tumors in mice which resulted in significant inhibition of tumor growth. The inhibitory effects of pmIL-12/PPC were enhanced when combined with specific chemotherapeutic agents, demonstrating the potential usefulness of pIL-12/PPC as an adjuvant therapy for cancer treatment.
Fewell
Jason G
JG
Expression Genetics, Inc., Huntsville, AL 35801, USA. Jfewell@egencorp.com
Matar
Majed
M
Slobodkin
Gregory
G
Han
Sang-Oh
SO
Rice
Jennifer
J
Hovanes
Bruce
B
Lewis
Danny H
DH
Anwer
Khursheed
K
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002784:Cholesterol / Q000737:chemistry; D003131:Combined Modality Therapy; D004247:DNA / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D007167:Immunotherapy / Q000379:methods*; D007376:Interleukin-2 / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009369:Neoplasms / Q000188:drug therapy / Q000628:therapy*; D023282:Nuclease Protection Assays; D010957:Plasmids / Q000235:genetics; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry; D014162:Transfection
D000970:Antineoplastic Agents; D007376:Interleukin-2; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D004247:DNA; D002784:Cholesterol