Novel Codon-Optimized Gene Therapeutic for Methylmalonic Acidemia

Methylmalonic Acidemia (MMA) is a metabolic disorder characterized by increased acidity in the blood and tissues due to toxic accumulation of protein and fat by-products resulting in seizures, strokes, and chronic kidney failure. A significant portion of MMA cases stem from a deficiency in a key mitochondrial enzyme, methylmalonyl-CoA mutase (MUT), required to break down amino acids and lipids. Currently, there are no treatments for MMA and the disease is managed primarily with dietary restriction of amino acid precursors and liver-kidney transplantation in severe cases.

The present invention describes a synthetic codon-optimized MUT gene (co-MUT) that improves expression of human methylmalonyl-CoA mutase. A series of novel gene therapy vectors containing co-MUT rescued MMA mice from lethality and lowered levels of methylmalonic acid in the blood. Results of pre-clinical efficacy studies demonstrate a promising therapy for MMA and other renal-associated disorders.

Potential Commercial Applications: Competitive Advantages:
  • The co-MUT transgene could be used to treat MMA patients.
  • In addition, it could be used to produce MUT in vitro for MMA enzyme replacement therapy.
  • co-MUT transgene could be used through non-viral and viral gene delivery.

Development Stage:
  • In vitro data available
  • In vivo data available (animal)


Charles Venditti (NHGRI)  ➽ more inventions...

Randy Chandler (NHGRI)  ➽ more inventions...

Intellectual Property:
US Pat: 9,719,080 issued 2017-08-01
US Pat: 10,307,469 issued 2019-06-04
PCT Application No. PCT/2014/028045 filed on 2014-03-14
US Application No. 15/633,964 filed on 2017-06-27
US Application No. 16/390,917 filed on 2019-04-22

Collaboration Opportunity:

The Organic Acid Research Section at the National Human Genome Research Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize codon-optimized MUT constructs. For collaboration opportunities, please contact Claire T. Driscoll at

Licensing Contact:
Eggerton Campbell, Ph.D.
Phone: 301-402-1648

OTT Reference No: E-243-2012-0
Updated: Oct 27, 2014