Effect of rapamycin on immunity induced by vector-mediated dystrophin expression in mdx skeletal muscle.

Scientific Reports
Saman EghtesadP R Clemens

Abstract

Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene. Therapeutic gene replacement of a dystrophin cDNA into dystrophic muscle can provide functional dystrophin protein to the tissue. However, vector-mediated gene transfer is limited by anti-vector and anti-transgene host immunity that causes rejection of the therapeutic protein. We hypothesized that rapamycin (RAPA) would diminish immunity due to vector-delivered recombinant dystrophin in the adult mdx mouse model for DMD. To test this hypothesis, we injected limb muscle of mdx mice with RAPA-containing, poly-lactic-co-glycolic acid (PLGA) microparticles prior to dystrophin gene transfer and analyzed treated tissue after 6 weeks. RAPA decreased host immunity against vector-mediated dystrophin protein, as demonstrated by decreased cellular infiltrates and decreased anti-dystrophin antibody production. The interpretation of the effect of RAPA on recombinant dystrophin expression was complex because of an effect of PLGA microparticles.

References

Jan 1, 1991·Molecular Aspects of Medicine·E P Hoffman, L Schwartz
Jan 1, 1991·Neuromuscular Disorders : NMD·A E Emery
May 26, 1990·Lancet·A E Emery
Feb 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·G BulfieldK J Moore
Feb 15, 1995·Transplantation·J T VilquinJ P Tremblay
Nov 1, 1996·Human Molecular Genetics·Y YangJ M Wilson
Nov 9, 2000·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·B J ChenN J Chao
Jun 16, 2001·Molecular Therapy : the Journal of the American Society of Gene Therapy·Z L JiangP R Clemens
Dec 12, 2001·Molecular Therapy : the Journal of the American Society of Gene Therapy·D Hartigan-O'ConnorJ S Chamberlain
Mar 28, 2002·International Journal of Sport Nutrition and Exercise Metabolism·J C Lawrence
Sep 17, 2002·Molecular Therapy : the Journal of the American Society of Gene Therapy·Soyoung C GilchristPaula R Clemens
Sep 25, 2002·Proceedings of the National Academy of Sciences of the United States of America·Christiana DelloRussoJeffrey S Chamberlain
Dec 24, 2002·Archives of Disease in Childhood·E P ParsonsA J Clarke
Oct 31, 2003·Expert Reviews in Molecular Medicine·Dominic J WellsKim E Wells
Sep 29, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Zhilong JiangPaula R Clemens
Dec 14, 2004·Journal of Controlled Release : Official Journal of the Controlled Release Society·Lei Li, Steven P Schwendeman
Mar 5, 2005·Blood·Manuela BattagliaMaria-Grazia Roncarolo
Apr 9, 2005·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Nanda KerkarSukru Emre
Oct 19, 2005·Gene Therapy·R AlbaM Chillon
Sep 23, 2006·Physiology·Xuemin Wang, Christopher G Proud
Dec 22, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Laura StraussAlfred Zippelius
Feb 8, 2007·American Journal of Physiology. Endocrinology and Metabolism·Amanda A Hayashi, Christopher G Proud
May 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Heth R TurnquistAngus W Thomson
Nov 13, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·S JhunjhunwalaS R Little
Oct 7, 2009·Transplant International : Official Journal of the European Society for Organ Transplantation·Christian M LangeTim O Hirche
May 25, 2011·Molecular Medicine·Saman EghtesadPaula R Clemens

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Methods Mentioned

BETA
electrophoresis
Cytomation

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.