Anti-JL1 antibody-conjugated poly (L-lysine) for targeted gene delivery to leukemia T cells.
We have designed the gene delivery carrier targeted to Molt 4 cells, human leukemia T cells, using monoclonal antibody against leukemia-specific JL1 antigen, anti-JL1 antibody, as a targeting moiety. Anti-JL1 antibody has been proven to bind to JL1 antigen and subsequently be internalized into Molt 4 cells, demonstrating that anti-JL1 antibody has the potential as a targeting ligand for leukemia-specific gene transfer. Anti-JL1 antibody was modified with the heterobifunctional crosslinker, PDPH, at carbohydrate sites and conjugated to thiolated poly-L-lysine (PLL) via disulfide bridges. The composition and antigen binding affinity of antibody-PLL conjugates were analyzed by the amino acid analysis and the flow cytometry, respectively. Antibody-PLL conjugates neutralized pSV-beta-galactosidase plasmid DNA at 5:1 weight ratio and condensed into about 200--300-nm complexes. DNA/antibody-PLL complexes were effectively internalized into Molt 4 cells after 4 h incubation at 37 degrees C and showed significantly higher in vitro transfection efficiency than DNA/PLL complexes and DNA/Lipofectin formulation due to the targeting effect of receptor-mediated endocytosis induced by anti-JL1 antibody.
Suh
W
W
Department of Pharmaceutics and Pharmaceutical Chemistry, Center for Controlled Chemical Delivery, BPRB Rm. 205, University of Utah, Salt Lake City, UT 84112, USA.
Chung
J K
JK
Park
S H
SH
Kim
S W
SW
D000596:Amino Acids / Q000032:analysis; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D000945:Antigens, Differentiation, T-Lymphocyte / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology; D000963:Antimetabolites / Q000627:therapeutic use; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D015774:Ganciclovir / Q000627:therapeutic use; D018390:Gene Targeting / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D015458:Leukemia, T-Cell / Q000235:genetics* / Q000276:immunology*; D008024:Ligands; D008027:Light; D018613:Microscopy, Confocal; D010957:Plasmids / Q000235:genetics; D011107:Polylysine / Q000008:administration & dosage / Q000737:chemistry*; D012542:Scattering, Radiation; D014162:Transfection / Q000379:methods*; D014407:Tumor Cells, Cultured
D000596:Amino Acids; D000945:Antigens, Differentiation, T-Lymphocyte; D000963:Antimetabolites; C114952:JL1 antigen; D008024:Ligands; D011107:Polylysine; D015774:Ganciclovir