Nuclear-targeted chimeric vector enhancing nonviral gene transfer into skeletal muscle of Fabry mice in vivo

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Matthieu D LavigneD C Górecki

Abstract

Poor nuclear entry, especially into nondividing cells, is a limiting factor in nonviral gene delivery. We have engineered a novel chimeric vector relying on the controlled assembly of a TAT-tagged multisubunit DNA binding protein (EcoR124I) with expression plasmids containing the EcoR124I recognition site. Molecular interactions of this molecular assembly were studied by electrophoretic mobility shift assay and atomic force microscopy. Maintenance of nanocomplexes in an appropriate stoichiometric ratio was both necessary and sufficient to produce a significant (>8-fold) increase in the activity of the therapeutic alpha-galactosidase A enzyme after intramuscular administration in the mouse model of Fabry disease. To our knowledge, this is the first molecular targeting system significantly enhancing plasmid-based expression in skeletal muscle. Coinjection with pluronic SP1017 produced further enhancement of gene expression, demonstrating cumulative effects of the increased nuclear delivery by TAT chimeras and transcription activation by the pluronic. Cell penetration peptides (CPP), such as TAT, have been shown to improve delivery of macromolecules, when linked directly. However, in our system TAT-enhanced targeting took place ev...Continue Reading

References

Apr 19, 1996·Journal of Molecular Biology·P JanscakK Firman
Mar 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·T OhshimaA B Kulkarni
Apr 29, 1998·The Journal of Biological Chemistry·H PollardD Escande
Jun 10, 1998·The EMBO Journal·D Görlich
Jan 6, 1999·Proceedings of the National Academy of Sciences of the United States of America·M A ZantaJ P Behr
Feb 18, 1999·Human Gene Therapy·J K UtvikK Gundersen
Mar 29, 2001·Molecular Therapy : the Journal of the American Society of Gene Therapy·N J CaronJ P Tremblay
May 11, 2001·The Journal of Biological Chemistry·A EguchiM Nakanishi
Jul 5, 2001·Proceedings of the National Academy of Sciences of the United States of America·V P TorchilinT S Levchenko
Jul 7, 2001·The New England Journal of Medicine·C M EngUNKNOWN International Collaborative Fabry Disease Study Group
Mar 15, 2002·BMC Developmental Biology·Arkady TorchinskyAmos Fein
Sep 6, 2002·Bioorganic & Medicinal Chemistry·Ching-Hsuan TungRalph Weissleder
Jul 5, 2003·Molecular Therapy : the Journal of the American Society of Gene Therapy·Mathias LundbergMagnus Johansson
Apr 30, 2004·Nature·Yaakov BenensonEhud Shapiro
Aug 10, 2004·Nature Structural & Molecular Biology·Ralf SeidelCees Dekker
Sep 8, 2004·Journal of Nanobiotechnology·Sivanand S PennadamDariusz C Górecki
Oct 14, 2004·Journal of the American Chemical Society·Sivanand S PennadamCameron Alexander
May 24, 2005·Gene Therapy·D A DeanW E Zimmer
Jun 25, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Matthieu D LavigneDariusz C Górecki
Oct 4, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Srikanth SriadibhatlaAlexander Kabanov
Oct 11, 2005·Journal of Controlled Release : Official Journal of the Controlled Release Society·Beverley R TwaitesCameron Alexander
Dec 21, 2005·American Journal of Reproductive Immunology : AJRI·Arkady TorchinskyVeadimir Toder
Mar 15, 2006·The Journal of Gene Medicine·Laurence VaysseCharles Coutelle
Mar 16, 2006·Bioconjugate Chemistry·Aparna ReniguntaJörg Hänze
Aug 11, 2006·The Journal of Gene Medicine·Samir El-AndaloussiUlo Langel
Aug 31, 2006·Expert Opinion on Emerging Drugs·Matthieu D Lavigne, Dariusz C Górecki
Aug 31, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Gisela TünnemannM Cristina Cardoso
Sep 12, 2006·The Journal of Clinical Investigation·Ana Toro, Eyal Grunebaum
Oct 26, 2006·Circulation Journal : Official Journal of the Japanese Circulation Society·Makoto YoshimitsuJeffrey A Medin
Nov 1, 2006·Current Gene Therapy·C TrolletP Bigey
Dec 13, 2006·Science·Georg SeeligErik Winfree

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Citations

Apr 12, 2013·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Aritz Perez Ruiz de GaribayAlicia Rodríguez-Gascón
Apr 7, 2010·Expert Opinion on Drug Delivery·Joana R ViolaC I Edvard Smith
May 14, 2009·Expert Opinion on Drug Delivery·Eugen BarbuDariusz C Górecki
Jul 27, 2010·Biotechnology Advances·Gabriel Kun Yung Wong, Andrew T Chiu
May 21, 2010·Biotechnology Advances·Gabriel Kun Yung Wong, Andrew T Chiu
Sep 10, 2020·International Journal of Molecular Sciences·Enrico P SpugniniAlfonso Baldi
Jun 15, 2011·Chembiochem : a European Journal of Chemical Biology·Hemanshu MundhadaUlrich Schwaneberg

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