Treatment of metabolic disorders using genomic technologies: Lessons from methylmalonic acidemia.
Leah E VenturoniCharles P VendittiPublished in: Journal of inherited metabolic disease (2022)
Hereditary methylmalonic acidemia (MMA) caused by deficiency of the enzyme methylmalonyl-CoA mutase (MMUT) is a relatively common and severe organic acidemia. The recalcitrant nature of the condition to conventional dietary and medical management has led to the use of elective liver and combined liver-kidney transplantation in some patients. However, liver transplantation is intrinsically limited by organ availability, the risks of surgery, procedural and life-long management costs, transplant comorbidities, and a remaining underlying risk of complications related to MMA despite transplantation. Here, we review pre-clinical studies that present alternative approaches to solid organ transplantation as a treatment for MMUT MMA, including adeno-associated viral gene addition therapy, mRNA therapy, and genome editing, with and without nuclease enhancement.
Keyphrases
- genome editing
- kidney transplantation
- crispr cas
- end stage renal disease
- chronic kidney disease
- newly diagnosed
- healthcare
- ejection fraction
- minimally invasive
- copy number
- genome wide
- gene expression
- peritoneal dialysis
- cell therapy
- prognostic factors
- coronary artery bypass
- patients undergoing
- combination therapy
- coronary artery disease
- bone marrow
- climate change
- dna methylation
- binding protein
- atrial fibrillation
- dna binding