Anti-GAD antibody targeted non-viral gene delivery to islet beta cells
作者： Ji Hoon Jeong , Minhyung Lee , Won Jong Kim , James W. Yockman , Tae Gwan Park
DOI: 10.1016/J.JCONREL.2005.07.010
关键词:
摘要: An islet cell targeting polymeric gene carrier was synthesized by conjugating anti-GAD Fab' fragment to PEI via PEG linker (PEI-PEG-Fab'). The prepared from a murine monoclonal antibody against glutamic acid decarboxylase (GAD), which has been identified as one of the major auto-antigens expressed in cells, and used moiety for targeting. electrophoretic migration plasmid DNA (pCMVLuc)/PEI-PEG-Fab' complexes agarose gel completely retarded above N/P ratio 2. demonstrated size 100-275 nm with an almost neutral surface charge. Confocal microscopy revealed that PEI-PEG-Fab' showed much higher cellular binding uptake efficiency compared PEI-PEG complexes. about 10-fold transfection (relative luciferase activity) than GAD-expressing mouse insulinoma cells (MIN6), however reduced GAD negative (293) presence competitive free Fab'. Considering charge its DNA, selectivity toward expressing specific antigen, conjugate could be thought potential candidate systemic therapy treatment type I diabetes.
nature.com
postech.ac.kr
elsevier.com参考文章(26)
Klaus Kunath, Anke von Harpe, Holger Petersen, Dagmar Fischer, Karlheinz Voigt, Thomas Kissel, Ulrich Bickel, The Structure of PEG-Modified Poly(Ethylene Imines) Influences Biodistribution and Pharmacokinetics of Their Complexes with NF-κB Decoy in Mice Pharmaceutical Research. ,vol. 19, pp. 810- 817 ,(2002) , 10.1023/A:1016152831963
J.L. Palmer, A. Nisonoff, Reduction and Reoxidation of a Critical Disulfide Bond in the Rabbit Antibody Molecule Journal of Biological Chemistry. ,vol. 238, pp. 2393- 2398 ,(1963) , 10.1016/S0021-9258(19)67983-4
Darin Y. Furgeson, James W. Yockman, Margit-Maria Janat, Sung Wan Kim, Tumor efficacy and biodistribution of linear polyethylenimine-cholesterol/DNA complexes. Molecular Therapy. ,vol. 9, pp. 837- 845 ,(2004) , 10.1016/J.YMTHE.2004.02.014
B E Faulkner-Jones, D S Cram, J Kun, L C Harrison, Localization and quantitation of expression of two glutamate decarboxylase genes in pancreatic beta-cells and other peripheral tissues of mouse and rat Endocrinology. ,vol. 133, pp. 2962- 2972 ,(1993) , 10.1210/ENDO.133.6.8243324
Antoine Kichler, Miguel Chillon, Christian Leborgne, Olivier Danos, Benoı̂t Frisch, Intranasal gene delivery with a polyethylenimine-PEG conjugate. Journal of Controlled Release. ,vol. 81, pp. 379- 388 ,(2002) , 10.1016/S0168-3659(02)00080-9
W A Hagopian, C B Sanjeevi, I Kockum, M Landin-Olsson, A E Karlsen, G Sundkvist, G Dahlquist, J Palmer, A Lernmark, Glutamate decarboxylase-, insulin-, and islet cell-antibodies and HLA typing to detect diabetes in a general population-based study of Swedish children. Journal of Clinical Investigation. ,vol. 95, pp. 1505- 1511 ,(1995) , 10.1172/JCI117822
Wonhee Suh, June-Key Chung, Seong-Hoe Park, Sung Wan Kim, Anti-JL1 antibody-conjugated poly (l-lysine) for targeted gene delivery to leukemia T cells Journal of Controlled Release. ,vol. 72, pp. 171- 178 ,(2001) , 10.1016/S0168-3659(01)00273-5
Julia Kloeckner, Lina Prasmickaite, Anders HØgset, Kristian Berg, Ernst Wagner, Photochemically enhanced gene delivery of EGF receptor-targeted DNA polyplexes. Journal of Drug Targeting. ,vol. 12, pp. 205- 213 ,(2004) , 10.1080/10611860410001723090
Francesca Ungaro, Giuseppe De Rosa, Agnese Miro, Fabiana Quaglia, Spectrophotometric determination of polyethylenimine in the presence of an oligonucleotide for the characterization of controlled release formulations. Journal of Pharmaceutical and Biomedical Analysis. ,vol. 31, pp. 143- 149 ,(2003) , 10.1016/S0731-7085(02)00571-X
Christian Plank, Karl Mechtler, Francis C. Szoka, Ernst Wagner, Activation of the Complement System by Synthetic DNA Complexes: A Potential Barrier for Intravenous Gene Delivery Human Gene Therapy. ,vol. 7, pp. 1437- 1446 ,(1996) , 10.1089/HUM.1996.7.12-1437