Controlled removal of a nonviral episomal vector from transfected cells

Gene
Sina RupprechtHans Lipps

Abstract

An ideal vector to be used in gene therapy should allow long-term and regulated expression of the therapeutic sequence, but in many cases, it would be most desirable to remove all ectopic vector sequences from the cell once expression is no longer required. The vector pEPI is the first nonviral autonomous replicon that was constructed for mammalian cells. It represents a minimal model system to study the epigenetic regulation of replication and transcription but is also regarded as a promising alternative to currently used viral vector systems in gene therapy. Its function relies on a transcription unit linked to an S/MAR sequence. We constructed an inducible pEPI vector system based on the Tet ON system in which transcription is switched on in the presence of doxycycline. We show that for vector replication and long-term maintenance an ongoing transcription running into the S/MAR element is required. Once established, the vector is lost from the cell upon switching off transcription from the gene linked to the S/MAR. This feature provides not only controlled transgene expression but also the possibility to remove all vector molecules from the cells upon demand. This inducible episomal nonviral vector system will find broad app...Continue Reading

References

Jun 14, 1967·Journal of Molecular Biology·B Hirt
Jun 22, 2000·Proceedings of the National Academy of Sciences of the United States of America·S UrlingerW Hillen
Mar 17, 2001·Genesis : the Journal of Genetics and Development·M T HasanH Bujard
Dec 20, 2003·The EMBO Journal·Daniel SchaarschmidtRolf Knippers
Jul 24, 2004·Proceedings of the National Academy of Sciences of the United States of America·Andreas C W JenkeHans J Lipps
Jun 11, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·S GoverdhanaM G Castro
Nov 9, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Isabelle BardeOlivier Danos
Jun 21, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Dean A JacksonHans J Lipps
Nov 15, 2006·Proceedings of the National Academy of Sciences of the United States of America·Stefano ManziniMarialuisa Lavitrano
Jan 25, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Minh NguyenThomas C Harding
Aug 9, 2007·BMC Cell Biology·Isa M StehleHans J Lipps
Mar 3, 2009·Journal of Molecular Biology·Aristeidis GiannakopoulosAglaia Athanassiadou
Apr 28, 2009·Advanced Drug Delivery Reviews·Knut StiegerFabienne Rolling
May 14, 2009·Cancer Research·Michael R LoebingerSam M Janes
May 1, 2010·Biomolecular Concepts·Claudia HagedornSina Rupprecht

❮ Previous
Next ❯

Citations

Sep 5, 2013·Molecular Therapy. Nucleic Acids·Claudia HagedornHans J Lipps
Jun 8, 2011·Human Gene Therapy·Claudia HagedornHans J Lipps
Jun 6, 2013·BMC Biotechnology·Rudolf HaaseManfred Ogris
Jan 30, 2014·Nucleic Acids Research·Santhosh Chakkaramakkil VerghesePeter Kurre
May 10, 2011·Expert Opinion on Biological Therapy·Orestis ArgyrosRichard P Harbottle
Jun 14, 2017·Nucleic Acids Research·Claudia HagedornHans J Lipps
May 19, 2020·Molecular Therapy. Methods & Clinical Development·Matthias BozzaRichard P Harbottle
Aug 6, 2021·Human Gene Therapy·Grace Elizabeth MuliaMarxa Leão Figueiredo
Jun 5, 2012·Cold Spring Harbor Protocols·Claudia HagedornHans J Lipps

❮ Previous
Next ❯

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Related Papers

Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology
Federico TessadoriRoel van Driel
Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte
O ArgyrosRichard Harbottle
Proceedings of the National Academy of Sciences of the United States of America
Stefano ManziniMarialuisa Lavitrano
© 2021 Meta ULC. All rights reserved