Gene transfer with a vector expressing Maxi-K from a smooth muscle-specific promoter restores erectile function in the aging rat

Gene Therapy
Arnold MelmanG J Christ

Abstract

Previous reports have demonstrated that gene transfer with the alpha, or pore-forming, subunit of the human Maxi-K channel (hSlo) restores the decline in erectile capacity observed in established rat models of diabetes and aging. Preliminary data from a human clinical trial also showed safety and potential efficacy in 11 men treated with the same plasmid construct expressing the Maxi-K channel. In all instances, the original plasmid was driven by the heterologous cytomegalovirus promoter which is broadly active in a wide variety of cell and tissue types. To more precisely determine the contribution of the corporal myocyte to the observed physiological effects in vivo, we report here our initial work using a distinct vector (pSMAA-hSlo) in which hSlo gene expression was driven off the mouse smooth muscle alpha-actin (SMAA) promoter. Specifically, older rats, with diminished erectile capacity, were given a single intracorporal injection with either 100 mug pVAX-hSlo or 10, 100 or 1000 mug pSMAA-hSlo, or vector or vehicle alone. Significantly increased intracavernous pressure (ICP) responses to cavernous nerve stimulation were observed for all doses of both plasmids encoding hSlo, relative to control injections. These data confirm...Continue Reading

References

May 1, 1993·The Journal of Urology·S E LernerG J Christ
Feb 26, 1999·The Journal of Urology·A Melman, J C Gingell
Mar 10, 2001·International Journal of Urology : Official Journal of the Japanese Urological Association·K MarumoM Murai
Feb 19, 2002·International Journal of Impotence Research·E Wespes
Jul 31, 2002·Heart Disease·Arnold Melman, George J Christ
Oct 16, 2002·Vascular Pharmacology·Victoria P Korovkina, Sarah K England
May 15, 2004·American Journal of Physiology. Gastrointestinal and Liver Physiology·Andrew W KnottBrad W Warner
Sep 3, 2004·Journal of the American Geriatrics Society·Andre B AraujoJohn B McKinlay
Sep 17, 2004·American Journal of Physiology. Heart and Circulatory Physiology·George J ChristArnold Melman
Mar 11, 2005·Advanced Drug Delivery Reviews·Alain Rolland
May 1, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Tracy J PritchardRichard J Paul

❮ Previous
Next ❯

Citations

Sep 17, 2011·Current Urology Reports·Eric Chung, Gerald B Brock
Aug 23, 2011·Journal of Biosciences·Wing-Fu Lai
Feb 4, 2011·International Journal of Impotence Research·J M JohnsonB Musicki
Jun 24, 2011·American Journal of Physiology. Cell Physiology·Kiril L HristovGeorgi V Petkov
Aug 7, 2009·American Journal of Physiology. Cell Physiology·Nirmala Devi KanikaKelvin Paul Davies
May 16, 2008·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Matthias E WernerMark T Nelson
Jul 29, 2010·Expert Opinion on Biological Therapy·Naoki YoshimuraJoseph C Glorioso
Sep 25, 2012·The Journal of Urology·Natalya A Lopushnyan, Kanchan Chitaley
Nov 6, 2010·The Journal of Sexual Medicine·Francois GiulianoKim Wallen
Oct 30, 2010·The Journal of Sexual Medicine·Arthur L BurnettZhong C Xin
May 12, 2009·Molecular and Cellular Endocrinology·Rowena G ChuaKelvin P Davies
Sep 2, 2015·Nitric Oxide : Biology and Chemistry·Serap GurWayne J G Hellstrom
Sep 30, 2016·Expert Opinion on Pharmacotherapy·Igor VoznesenskyWayne J G Hellstrom
Jul 25, 2012·Nature Reviews. Urology·Lukman HakimMaarten Albersen
Dec 20, 2013·American Journal of Physiology. Cell Physiology·Kiril L HristovGeorgi V Petkov
Jun 8, 2017·The Aging Male : the Official Journal of the International Society for the Study of the Aging Male·Ecem KayaSerap Gur
Jul 1, 2013·Journal of Clinical Urology·Jas Kalsi, Asif Muneer
Jun 12, 2021·Therapeutics and Clinical Risk Management·Karl-Erik AnderssonArnold Melman

❮ 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.