- Gene Therapy Vector Successfully Delivers shRNA Into Liver Cells
Amsterdam Molecular Therapeutics (Euronext: AMT) a world leader in gene therapy, today reported positive preclinical data from a study using an AAV gene therapy product to lower cholesterol. The data show that a single dose of the gene therapy carrying a short hairpin RNA to silence Apolipoprotein B100 (ApoB100), resulted in a reduction of serum cholesterol of approximately 80%, without any signs of toxicity. These data validate AMT's technology platform as a powerful tool for successful gene silencing within target cells. The data were presented by Annemart Koorneef, scientist at AMT, yesterday during the 13th Annual American Society of Gene and Cell Therapy (ASGCT) Meeting in Washington, DC.
"With just a single dose of our cholesterol targeting gene therapy, a long-lasting, significant reduction of serum cholesterol is achieved. This preliminary study suggest that AMT's technology may have overcome one of the major problems of shRNA therapies, namely efficient and non-toxic intracellular delivery," noted Jorn Aldag, CEO of Amserdam Molecular Therapeutics.
In the study, AMT used its proprietary AAV-based platform to efficiently deliver a shRNA that silences both human and mouse Apolipoprotein B100 (ApoB100). A single intravenous administration caused prolonged ApoB100 gene silencing that was sequence-specific and not associated with liver toxicity, oversaturation of the cellular miRNA machinery or induction of immune responses. In addition, it was shown that the shRNA constructs against ApoB100 specifically and efficiently silence human ApoB100 ex vivo.
ApoB100 is the structural protein of Low Density Lipoprotein (LDL) particles that carry cholesterol. Silencing of ApoB100 with shRNAs results in a reduction of LDL-cholesterol and has the potential to be used to treat hypercholesterolaemia and cardiovascular disease.
SOURCE Amsterdam Molecular Therapeutics B.V