Persistent gene therapy in muscle may not require immunosuppression

Successful gene therapy is based on the effective delivery and maintained expression of healthy copies of a gene into tissues of individuals with a disease-associated genetic mutation. Recombinant adeno-associated virus (rAAV) vectors have shown promise in early clinical trials as effective therapies for several genetic diseases, including Leber congenital amaurosis, Parkinson disease, and hemophilia.

Unfortunately, delivery of rAAV vectors to tissues other than the retina and CNS often results in development of an immune response against the viral capsid. The development of a neutralizing response against the rAAV vector prevents sustained expression of the healthy gene in the absence of immunosuppression.

In this issue of the Journal of Clinical Investigation, Christian Mueller and colleagues at the University of Massachusetts Medical School evaluated the persistence of rAAV-mediated expression the gene encoding M-type α-1 antitrypsin (M-AAT) in patients that were AAT deficient. Patients received multiple intramuscular doses without immunosuppression, and M-ATT expression was evaluated in muscle biopsies. The authors determined that subjects sustained M-ATT expression in muscle tissue for at least one year, despite an initial influx of immune cells. Further evaluation of muscle fibers revealed a substantial population of regulatory T cells in patients with persistent M-ATT expression.

Together, the results from this study suggests that delivery of an M-ATT-encoding rAAV vector promotes a regulatory that allows for long term that does not require immune suppression.

More information: J Clin Invest. DOI: 10.1172/JCI70314

Related Stories

Researchers identify way to increase gene therapy success

date Oct 30, 2013

Scientists in The Research Institute at Nationwide Children's Hospital have found a way to overcome one of the biggest obstacles to using viruses to deliver therapeutic genes: how to keep the immune system from neutralizing ...

Targeted gene therapy enhances treatment for Pompe disease

date Jun 25, 2012

Gene therapy to replace the protein missing in Pompe disease can be effective if the patient's immune system does not react against the therapy. Targeted delivery of the gene to the liver, instead of throughout the body,suppresses ...

Recommended for you

Genetic testing in kids is fraught with complications

date Jul 02, 2015

A woman coping with the burden of familial breast cancer can't help but wonder if her young daughter will suffer the same fate. Has she inherited the same disease-causing mutation? Is it best to be prepared ...

Cause of acute liver failure in young children discovered

date Jul 02, 2015

Acute liver failure is a rare yet life-threatening disease for young children. It often occurs extremely rapidly, for example, when a child has a fever. Yet in around 50 percent of cases it is unclear as to why this happens. ...

Genome sequencing illuminates rare Aicardi syndrome

date Jul 02, 2015

As my inbox fills with ever more updates on the number of human genomes sequenced and the plummeting time and cost of next next next generation sequencing, I find myself hitting delete more and more often. ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.