Intravesical treatment of advanced urothelial bladder cancers with oncolytic HSV-1 co-regulated by differentially expressed microRNAs

Gene Therapy
K-X ZhangW W Jia

Abstract

Urothelial bladder cancer is the most common malignancy of the urinary tract. Although most cases are initially diagnosed as non-muscle-invasive, more than 80% of patients will develop recurrent or metastatic tumors. No effective therapy exists currently for late-stage metastatic tumors. By intravesical application, local administration of oncolytic Herpes Simplex virus (oHSV-1) can provide a promising new therapy for this disease. However, its inherent neurotoxicity has been a perceived limitation for such application. In this study, we present a novel microRNA-regulatory approach to reduce HSV-1-induced neurotoxicity by suppressing viral replication in neurons while maintaining oncolytic selectivity toward urothelial tumors. Specifically, we designed a recombinant virus that utilizes differentially expressed endogenous microR143 (non-cancerous, ubiquitous) and microR124 (neural-specific) to regulate expression of ICP-4, a gene essential for HSV-1 replication. We found that expression of ICP-4 must be controlled by a combination of both miR143 and miR124 to achieve the most effective attenuation in HSV-1-induced toxicity while retaining maximal oncolytic capacity. These results suggest that interaction between miR143 and miR12...Continue Reading

References

Oct 15, 2005·Development·Tingting Du, Phillip D Zamore
Oct 19, 2005·Gene Therapy·Alberto L Epstein
Nov 30, 2005·Nucleic Acids Research·Caifu ChenKarl J Guegler
May 3, 2006·Biological & Pharmaceutical Bulletin·Yukihiro AkaoTomoki Naoe
Jun 1, 2006·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Monika DeoDavid L Turner
Oct 31, 2006·Trends in Molecular Medicine·Ramiro GarzonCarlo M Croce
May 8, 2007·Nature Clinical Practice. Urology·Guido Dalbagni
Aug 19, 2007·Cell Research·Tingting Du, Phillip D Zamore
Nov 6, 2007·Frontiers in Bioscience : a Journal and Virtual Library·Tomoki Todo
Jul 23, 2008·Current Genomics·Torrisani JérômeCordelier Pierre
Oct 24, 2008·Glia·Angélique ColinNicole Déglon
Feb 28, 2009·Clinical Chemistry·Claudine L Bartels, Gregory J Tsongalis
Mar 17, 2009·Oligonucleotides·Angie ChengSusan Magdaleno
Apr 25, 2009·Journal of Cellular Physiology·Gaspare La RoccaRenato Baserga
Aug 13, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Cleo Y F LeeWilliam W G Jia
Feb 25, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Cleo Y F LeeWilliam W G Jia
Mar 25, 2010·Cancer Research·Xueqin ChenQiao Zhou
Jul 31, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kevin J HarringtonChristopher M Nutting
Mar 2, 2011·Nature Reviews. Drug Discovery
Mar 19, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jay B ShahColin P N Dinney
May 3, 2011·Methods in Molecular Biology·Erika Varkonyi-Gasic, Roger P Hellens
Nov 15, 2011·The Journal of Steroid Biochemistry and Molecular Biology·Minako SakuraiHironobu Sasano
Jan 13, 2012·CA: a Cancer Journal for Clinicians·Rebecca SiegelAhmedin Jemal
Jun 30, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Malin ÅkerblomJohan Jakobsson
Jul 31, 2012·Current Opinion in Urology·Sima P Porten, Matthew R Cooperberg
Aug 11, 2012·European Urology·Maximilian BurgerYair Lotan

❮ Previous
Next ❯

Citations

Dec 14, 2018·Oncoimmunology·Jonathan G PolLorenzo Galluzzi
Jul 22, 2019·Molecular Diagnosis & Therapy·Qi LiJunling Shi

❮ 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.