Available Technology

Tagged Form of Mut Enzyme and Its Use in Gene Therapy

Investigators at the National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH) are seeking collaborators to further develop gene therapy to treat methylmalonic acidemia (MMA). MMA is an autosomal recessive disorder, caused by the deficiency of the mitochondrial enzyme methylmalonyl-CoA mutase (MUT). It is characterized by metabolic instability, multi-organ pathology, and poor prognosis for long-term survival. The disease can lead to seizures, strokes, and kidney failure and is currently controlled mainly with dietary restrictions, although elective liver, kidney, or combined kidney/liver transplantation are also used to stabilize the most severely affected patients. Even though MMA is rare, all babies born in the United States are screened for this condition as newborns. NHGRI investigators have generated tagged constructs of Mut enzyme. The tag preserves enzyme processing but does not interfere with its activity and thus can be used to track the level of protein expression. One use for these constructs would be to track efficacy of gene therapy constructs that would deliver MUT gene to the affected individuals, for example, adeno-associated viral (AAV) gene therapy.
Patent Abstract: 
Investigators at the National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH) are seeking collaborators to further develop gene therapy to treat methylmalonic acidemia (MMA). MMA is an autosomal recessive disorder, caused by the deficiency of the mitochondrial enzyme methylmalonyl-CoA mutase (MUT). It is characterized by metabolic instability, multi-organ pathology, and poor prognosis for long-term survival. The disease can lead to seizures, strokes, and kidney failure and is currently controlled mainly with dietary restrictions, although elective liver, kidney, or combined kidney/liver transplantation are also used to stabilize the most severely affected patients. Even though MMA is rare, all babies born in the United States are screened for this condition as newborns. NHGRI investigators have generated tagged constructs of Mut enzyme. The tag preserves enzyme processing but does not interfere with its activity and thus can be used to track the level of protein expression. One use for these constructs would be to track efficacy of gene therapy constructs that would deliver MUT gene to the affected individuals, for example, adeno-associated viral (AAV) gene therapy.
Benefits 
Optimized to work for intra-mitochondrial proteins. -Shown to work in animal (murine) models.
applications 
Inventors: 
Charles Venditti
Patent Number: 
PCT/US2016/028974 US Application No. 62/152,520
Internal Laboratory Ref #: 
E-090-2015/0
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