Therapeutic level of functional human alpha 1 antitrypsin (hAAT) secreted from murine muscle transduced by adeno-associated virus (rAAV1) vector

The Journal of Gene Medicine
Yuanqing LuSihong Song

Abstract

Alpha 1 antitrypsin (AAT) is a serine proteinase inhibitor (serpin). One well-known function of this protein is to inactivate neutrophil elastase and other neutrophil-derived proteinases, and prevent the destruction of pulmonary extracellular matrix. Deficiency of AAT can cause emphysema due to degradation of interstitial elastin by elastase. The majority of circulating AAT is secreted from the liver. Muscle-directed gene therapy using recombinant adeno-associated virus 2 (rAAV2) vectors has been tested to increase the serum levels of AAT. However, inefficient transduction of rAAV2 vector makes it difficult to reach therapeutic levels of AAT in clinical trials and it remains unclear as to whether muscle-secreted AAT is functional. In the present study, we evaluated five serotypes (1, 2, 3, 4, and 5) of rAAV vectors for transduction efficiency in mouse muscle. Results from these studies showed that rAAV1 is the most efficient vector among these serotypes and mediated at least 100-fold higher levels of AAT secretion than the rAAV2 vector. Western blot analysis showed that this murine muscle-secreted human AAT (hAAT) formed a complex with human neutrophil elastase in a dose-dependent manner. An anti-elastase activity assay showed ...Continue Reading

Associated Clinical Trials

References

Jan 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·M A KayW Pokorny
Apr 23, 1987·The New England Journal of Medicine·M D WewersR G Crystal
Nov 1, 1987·Journal of Applied Physiology·M A CasolaroG Kawasaki
Nov 15, 1994·Biochemical and Biophysical Research Communications·S F AliñoA Crespo
Apr 1, 1994·American Journal of Respiratory Cell and Molecular Biology·Y SetoguchiR G Crystal
Jan 1, 1994·American Journal of Respiratory Cell and Molecular Biology·A E CanonicoK L Brigham
Nov 13, 1998·Journal of Virology·W XiaoJ M Wilson
Nov 25, 1998·Proceedings of the National Academy of Sciences of the United States of America·S SongT R Flotte
Apr 10, 1999·Journal of Virology·W XiaoJ M Wilson
Dec 22, 2000·Molecular Therapy : the Journal of the American Society of Gene Therapy·H ChaoC E Walsh
Jan 10, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·L ShapiroA H Ralston
Mar 29, 2001·Proceedings of the National Academy of Sciences of the United States of America·S SongT R Flotte
Nov 5, 2002·The Journal of Biological Chemistry·Andrew S RobertsonTimothy R Dafforn
Apr 2, 2003·Molecular Therapy : the Journal of the American Society of Gene Therapy·Bernd HauckWeidong Xiao
Feb 10, 2004·Proceedings of the National Academy of Sciences of the United States of America·Sihong SongTerence R Flotte
Sep 11, 2004·Biochemical and Biophysical Research Communications·Sabina JanciauskieneTim Stevens
Sep 24, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Sihong SongByron E Petersen
Aug 12, 2005·Proceedings of the National Academy of Sciences of the United States of America·Eli C LewisCharles A Dinarello

❮ Previous
Next ❯

Citations

Jun 19, 2013·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Alice M Turner
Apr 8, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Christine L HalbertA Dusty Miller
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Yuanqing Lu, Sihong Song
Feb 14, 2009·International Journal of Medical Sciences·Waldemar WaldeckKlaus Braun
Oct 11, 2007·Pharmacogenomics·Pedro E CruzTerence R Flotte
Oct 27, 2007·Expert Opinion on Biological Therapy·Simona MarzoratiCamillo Ricordi
Nov 5, 2014·Expert Opinion on Biological Therapy·Heather S Loring, Terence R Flotte
Dec 1, 2012·Journal of Immunological Methods·Guo-Jie YeJeffrey D Chulay
Apr 1, 2008·Transplantation Proceedings·R D MolanoL Inverardi
Nov 7, 2013·Human Gene Therapy. Clinical Development·Maria J ChiuchioloRonald G Crystal
Jun 20, 2007·Journal of Cellular Physiology·Terence R Flotte
Jun 13, 2015·Human Gene Therapy Methods·Alisha M Gruntman, Terence R Flotte
Dec 21, 2010·Journal of Hepatology·Hong LiSihong Song
Jan 2, 2014·Trends in Molecular Medicine·Robert A Stockley, Alice M Turner
Aug 27, 2016·Annals of the American Thoracic Society·Maria J Chiuchiolo, Ronald G Crystal
Nov 20, 2016·Human Gene Therapy. Clinical Development·Thomas J ConlonBarry J Byrne
Jan 20, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ziv SandalonHaim Burstein
Dec 9, 2016·Human Gene Therapy·Dolan SondhiRonald G Crystal
Dec 17, 2008·Journal of Perinatology : Official Journal of the California Perinatal Association·D J Askew, G A Silverman
Jun 27, 2007·Laboratory Investigation; a Journal of Technical Methods and Pathology·Pedro E CruzTerence R Flotte
Aug 3, 2007·Respiration; International Review of Thoracic Diseases·Alice M Wood, Robert A Stockley
Apr 19, 2011·Nature Reviews. Genetics·Federico Mingozzi, Katherine A High
May 18, 2020·Advanced Drug Delivery Reviews·Tao Wan, Yuan Ping

❮ 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.