title: Dendritic alpha,epsilon-poly(L-lysine)s as delivery agents for antisense oligonucleotides.
abstract: OBJECTIVE
  To evaluate the potential use of dendritic alpha,epsilon-poly(L-lysine)s (DPL) for the efficient cellular delivery of antisense oligonucleotides.
  
  
  METHODS
  A series of dendritic alpha,epsilon-polylysines of various generations were prepared. Their physical properties and the ability to form complex with oligonucleotide were investigated by polyacrylamide gel electrophoresis, capillary zone electrophoresis (CZE), agarose gel electrophoresis, fluorescence titration and atomic force microscopy (AFM). The efficiency to deliver oligonucleotide to HeLa cells, stably transfected with plasmid pLuc/705, was evaluated by using antisense splicing correction assay and confocal microscopy.
  
  
  RESULTS
  DPLs formed the complexes with antisense oligonucleotide with modest cytotoxicity. The charge ratio of oligonucleotide to DPL and the size (generation) of DPLs were all critical variables for the antisense effect. Compared to low generation DPLs, high generation DPLs were more effective in delivering oligonucleotide into cells.
  
  
  CONCLUSIONS
  High generation DPL-oligonucleotide complexes were moderately effective for delivery antisense oligonucleotide. The complex formation provides a promise for in vivo therapeutic application of DPLs or their derivatives in the delivery of gene or oligonucleotide.
authors: Nanormics Inc., Sungbuk-gu, Seoul, 136-130, South Korea.
authors: Khee Dong
authors: KD
authors: Eom
authors: Sun Mi
authors: SM
authors: Park
authors: Huu Dung
authors: HD
authors: Tran
authors: Myong Soo
authors: MS
authors: Kim
authors: Ri Na
authors: RN
authors: Yu
authors: Hoon
authors: H
authors: Yoo
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry*; D004586:Electrophoresis; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D046911:Macromolecular Substances / Q000138:chemical synthesis / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008970:Molecular Weight; D016376:Oligonucleotides, Antisense / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D011073:Polyamines / Q000737:chemistry; D011107:Polylysine / Q000138:chemical synthesis / Q000737:chemistry*; D012326:RNA Splicing; D013050:Spectrometry, Fluorescence; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014162:Transfection / Q000379:methods
chemical_list: D050091:Dendrimers; D046911:Macromolecular Substances; D016376:Oligonucleotides, Antisense; C104700:PAMAM Starburst; D011073:Polyamines; D011107:Polylysine; D008156:Luciferases