Researchers from the University of Pennsylvania, Perelman School of Medicine, Gene Therapy Program, and Moderna, have shown that repeated administration of lipid nanoparticle-encapsulated mRNA therapy significantly extended survival and reduced serum leucine levels in a mouse model of maple syrup urine disease (MSUD). The researchers, led by James Wilson, M.D.
, Ph.D., from the University of Pennsylvania, Perelman School of Medicine, evaluated a lipid nanoparticle-based treatment approach to address all possible genetic mutations that can cause MSUD.
"Repeated intravenous delivery of lipid nanoparticle-encapsulated mRNAs encoding h BCKDHA, h BCKDHB , and h DBT increased survival and body weight, and decreased serum leucine levels in a hypomorphic MSUD mouse model that survives until weaning without clinical intervention," stated the investigators. "Repeated administration of LNP-encapsulated mRNAs may represent a potential long-term universal treatment approach for MSUD." In another new study emerging from Dr.
Wilson's laboratory, researchers identified a novel family of adeno-associated virus (AAV) variants with desirable biodistribution properties that may be useful for targeting tissues other than the liver, such as the heart. To improve the safety and cost of AAV gene therapy, capsid engineering efforts are aimed at redirecting in vivo AAV biodistribution away from the liver toward disease-relevant peripheral organs. One newly identified variant exhibited a six-fold reduct.