title: Enhanced splicing correction effect by an oligo-aspartic acid-PNA conjugate and cationic carrier complexes.
abstract: Peptide nucleic acids (PNAs) are synthetic structural analogues of DNA and RNA. They recognize specific cellular nucleic acid sequences and form stable complexes with complementary DNA or RNA. Here, we designed an oligo-aspartic acid-PNA conjugate and showed its enhanced delivery into cells with high gene correction efficiency using conventional cationic carriers, such as polyethylenimine (PEI) and Lipofectamine 2000. The negatively charged oligo-aspartic acid-PNA (Asp(n)-PNA) formed complexes with PEI and Lipofectamine, and the resulting Asp(n)-PNA/PEI and Asp(n)-PNA/Lipofectamine complexes were introduced into cells. We observed significantly enhanced cellular uptake of Asp(n)-PNA by cationic carriers and detected an active splicing correction effect even at nanomolar concentrations. We found that the splicing correction efficiency of the complex depended on the kind of the cationic carriers and on the number of repeating aspartic acid units. By enhancing the cellular uptake efficiency of PNAs, these results may provide a novel platform technology of PNAs as bioactive substances for their biological and therapeutic applications.
authors.affiliation: Department of Biochemistry, Chungnam National University, Daejeon 305-764, Republic of Korea; Laboratory for Advanced Molecular Probing, Research Center for Convergence Nanotechnology, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea.
authors.forename: Yun Mi
authors.initials: YM
authors.lastname: Bae
authors.affiliation: Department of Biochemistry, Chungnam National University, Daejeon 305-764, Republic of Korea; Catholic Research Institutes of Medical Science, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Myung Hee
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Gwang Sig
authors.initials: GS
authors.lastname: Yu
authors.affiliation: PANAGENE Inc., 816 Tamnip-dong, Yuseong-gu, Daejeon 305-510, Republic of Korea.
authors.forename: Bong Ho
authors.initials: BH
authors.lastname: Um
authors.affiliation: PANAGENE Inc., 816 Tamnip-dong, Yuseong-gu, Daejeon 305-510, Republic of Korea.
authors.forename: Hee Kyung
authors.initials: HK
authors.lastname: Park
authors.affiliation: PANAGENE Inc., 816 Tamnip-dong, Yuseong-gu, Daejeon 305-510, Republic of Korea.
authors.forename: Hyun-il
authors.initials: HI
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Gwangju Institute of Science and Technology (GIST), Gwangju 500-712, Republic of Korea.
authors.forename: Kang Taek
authors.initials: KT
authors.lastname: Lee
authors.affiliation: Laboratory for Advanced Molecular Probing, Research Center for Convergence Nanotechnology, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea; School of Chemical Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea. Electronic address: ydsuh@krict.re.kr.
authors.forename: Yung Doug
authors.initials: YD
authors.lastname: Suh
authors.affiliation: Department of Biochemistry, Chungnam National University, Daejeon 305-764, Republic of Korea. Electronic address: joonsig@cnu.ac.kr.
authors.forename: Joon Sig
authors.initials: JS
authors.lastname: Choi
mesh_terms: D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D002412:Cations / Q000378:metabolism; D004337:Drug Carriers / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008055:Lipids / Q000032:analysis; D020135:Peptide Nucleic Acids / Q000008:administration & dosage* / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011094:Polyethyleneimine / Q000378:metabolism; D012326:RNA Splicing; D014162:Transfection
chemical_list: D002412:Cations; D004337:Drug Carriers; D008055:Lipids; C086724:Lipofectamine; D020135:Peptide Nucleic Acids; D001224:Aspartic Acid; D011094:Polyethyleneimine
keywords: Lipofectamine; Peptide nucleic acid; Polyethylenimine; Splicing