AAV8-mediated expression of glucocerebrosidase ameliorates the storage pathology in the visceral organs of a mouse model of Gaucher disease

The Journal of Gene Medicine
Kerry Anne McEachernJohn Marshall

Abstract

Gaucher disease is the most common of the lysosomal storage disorders. The primary manifestation is the accumulation of glucosylceramide (GL-1) in the macrophages of liver and spleen (Gaucher cells), due to a deficiency in the lysosomal hydrolase glucocerebrosidase (GC). A Gaucher mouse model (D409V/null) exhibiting reduced GC activity and accumulation of GL-1 was used to evaluate adeno-associated viral (AAV)-mediated gene therapy. A recombinant AAV8 serotype vector bearing human GC (hGC) was administered intravenously to the mice. The levels of hGC in blood and tissues were determined, as were the effects of gene transfer on the levels of GL-1. Histopathological evaluation was performed on liver, spleen and lungs. Vector administration to pre-symptomatic Gaucher mice resulted in sustained hepatic secretion of hGC at levels that prevented GL-1 accumulation and the appearance of Gaucher cells in the liver, spleen and lungs. AAV administration to older mice with established disease resulted in normalization of GL-1 levels in the spleen and liver and partially reduced that in the lung. Analysis of the bronchoalveolar lavage fluid (BALF) from treated mice showed significant correction of the abnormal cellularity and cell differenti...Continue Reading

References

Dec 19, 1991·The New England Journal of Medicine·D ShoupeR A Lobo
Jul 1, 1990·The Biochemical Journal·J M AertsA W Schram
Apr 1, 1996·The Journal of Laboratory and Clinical Medicine·S P MillerN W Barton
Mar 4, 1998·European Journal of Immunology·P BertolinoC Rabourdin-Combe
Mar 14, 1998·Baillière's Clinical Haematology·E Sidransky, E I Ginns
Nov 24, 1998·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·C LiuJ A Barranger
Apr 10, 1999·The Journal of Biological Chemistry·T DoeringK Sandhoff
Sep 3, 1999·Quality of Life Research : an International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation·B J MasekD K Norman
Sep 22, 1999·Gene Therapy·N ChirmuleJ Wilson
May 12, 2000·Immunological Reviews·P A Knolle, G Gerken
Dec 1, 2001·Expert Opinion on Biological Therapy·J M Barranger, E A Novelli
Aug 6, 2002·Molecular Therapy : the Journal of the American Society of Gene Therapy·John MarshallSeng H Cheng
Aug 23, 2002·Proceedings of the National Academy of Sciences of the United States of America·Guang-Ping GaoJames M Wilson
Jan 4, 2003·Nature Reviews. Immunology·Ian Nicholas Crispe
Oct 28, 2003·The American Journal of Pathology·You-Hai XuGregory A Grabowski
Oct 30, 2003·Acta Haematologica·Alessandra D'Azzo
Dec 11, 2003·Molecular Therapy : the Journal of the American Society of Gene Therapy·Hee-Kyung Jin, Edward H Schuchman
Sep 17, 2004·Journal of Human Genetics·Young Bin HongSung-Chul Jung
Dec 9, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Baodong SunDwight D Koeberl
Feb 26, 2005·Annals of Neurology·Charles H ViteJohn H Wolfe
Aug 16, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Christine M BarbonSeng H Cheng

❮ Previous
Next ❯

Citations

Jan 12, 2011·Wiener medizinische Wochenschrift·Derralynn A Hughes, Gregory M Pastores
Apr 16, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Hua LiHildegund C J Ertl
Aug 26, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Gregory D HurlbutRonald K Scheule
Jun 30, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jennifer B NietupskiRonald K Scheule
Oct 20, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Huimin HuAlessandra d'Azzo
Dec 28, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Robin J ZieglerSeng H Cheng
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Yuanqing Lu, Sihong Song
Sep 29, 2011·Disease Models & Mechanisms·Tamar Farfel-BeckerAnthony H Futerman
Jan 7, 2011·Biologics : Targets & Therapy·Timothy M Cox
Jan 9, 2010·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Gregory M Pastores
Jul 9, 2008·World Journal of Gastroenterology : WJG·Ozgur Harmanci, Yusuf Bayraktar
May 23, 2007·Proceedings of the National Academy of Sciences of the United States of America·Marco A PassiniSeng H Cheng
Aug 2, 2014·The International Journal of Biochemistry & Cell Biology·Jenny Serra-VinardellJosefina Casas
Dec 10, 2008·Expert Opinion on Biological Therapy·Joel Charrow
Nov 2, 2006·Expert Opinion on Drug Delivery·Gregory A Grabowski
Dec 20, 2008·Lancet·Gregory A Grabowski
May 19, 2007·Molecular Genetics and Metabolism·Kerry Anne McEachernJohn Marshall
Nov 7, 2006·Molecular Genetics and Metabolism·Ellen SidranskyEdward I Ginns
May 28, 2008·Acta Paediatrica·Atul Mehta
Nov 17, 2010·American Journal of Hematology·Pramod K MistryGero Massenkeil
Nov 25, 2014·Expert Opinion on Therapeutic Targets·Einat B VitnerAnthony H Futerman
Apr 22, 2017·International Journal of Molecular Sciences·Dino Matias Santos, Gustavo Tiscornia
Feb 5, 2019·Journal of Inherited Metabolic Disease·Julien Baruteau, Simon N Waddington
Apr 19, 2011·Nature Reviews. Genetics·Federico Mingozzi, Katherine A High
Nov 21, 2017·Translational Science of Rare Diseases·Carlos R Ferreira, William A Gahl
Nov 22, 2013·The Annals of Pharmacotherapy·Lunawati L Bennett, Devipriya Mohan

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell-Type Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Cell-Type-Specific Viral Vectors (ASM)

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Cell-Type-Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

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.