Anti-JL1 antibody-conjugated poly (l-lysine) for targeted gene delivery to leukemia T cells

作者: Wonhee Suh , June-Key Chung , Seong-Hoe Park , Sung Wan Kim

DOI: 10.1016/S0168-3659(01)00273-5

关键词: DNAGene deliveryEndocytosisTransfectionAntibodyMonoclonal antibodyMolecular biologyLigand (biochemistry)BiochemistryIn vitroBiologyPharmaceutical Science

摘要: Abstract We have designed the gene delivery carrier targeted to Molt 4 cells, human leukemia T using monoclonal antibody against leukemia-specific JL1 antigen, anti-JL1 antibody, as a targeting moiety. Anti-JL1 has been proven bind antigen and subsequently be internalized into demonstrating that potential ligand for transfer. was modified with heterobifunctional crosslinker, PDPH, at carbohydrate sites conjugated thiolated poly- l -lysine (PLL) via disulfide bridges. The composition binding affinity of antibody–PLL conjugates were analyzed by amino acid analysis flow cytometry, respectively. Antibody–PLL neutralized pSV-β-galactosidase plasmid DNA 5:1 weight ratio condensed about 200–300-nm complexes. DNA/antibody–PLL complexes effectively cells after h incubation 37°C showed significantly higher in vitro transfection efficiency than DNA/PLL DNA/Lipofectin™ formulation due effect receptor-mediated endocytosis induced antibody.

参考文章(14)
Shyh-dar Li, Li-yuan Huang, None, Nonviral gene therapy: promises and challenges Gene Therapy. ,vol. 7, pp. 31- 34 ,(2000) , 10.1038/SJ.GT.3301110
Philip Marder, Lynn D. Apelgren, Thomas F. Bumol, Comparative analysis of monoclonal antibody-drug conjugate binding by flow cytometry Journal of Immunological Methods. ,vol. 96, pp. 165- 170 ,(1987) , 10.1016/0022-1759(87)90310-3
S H Park, Y M Bae, H J Kwon, T J Kim, J Kim, S J Lee, S K Lee, JL1, a novel differentiation antigen of human cortical thymocyte. Journal of Experimental Medicine. ,vol. 178, pp. 1447- 1451 ,(1993) , 10.1084/JEM.178.4.1447
WS Park, YM Bae, DH Chung, TJ Kim, EY Choi, J-K Chung, MC Lee, SY Park, MH Park, SH Park, A cell surface molecule, JL1; a specific target for diagnosis and treatment of leukemias Leukemia. ,vol. 12, pp. 1583- 1590 ,(1998) , 10.1038/SJ.LEU.2401161
P Erbacher, J-S Remy, J-P Behr, Gene transfer with synthetic virus-like particles via the integrin-mediated endocytosis pathway Gene Therapy. ,vol. 6, pp. 138- 145 ,(1999) , 10.1038/SJ.GT.3300783
Nadia Rosenthal, [72] Identification of regulatory elements of cloned genes with functional assays Methods in Enzymology. ,vol. 152, pp. 704- 720 ,(1987) , 10.1016/0076-6879(87)52075-4
Jin‐Seok Kim, Atsushi Maruyama, Toshihiro Akaike, Sung Wan Kim, Terplex DNA Delivery System As a Gene Carrier Pharmaceutical Research. ,vol. 15, pp. 116- 121 ,(1998) , 10.1023/A:1011917224044
Mien-chie Hung, Ernst Wagner, Leaf Huang, Nonviral vectors for gene therapy : Academic Press. ,(1999)