With CRISPR-Cas9 technology making its way toward clinical practice, laboratories are studying different gene-editing techniques, from base editors to prime editors, to correct mutations associated with various pathologies. Researchers at Tessera Therapeutics Inc. have been inspired by retrotransposons to develop a tool for editing DNA using RNA and reverse diseases such as phenylketonuria (PKU) or sickle cell disease (SCD).
New research shows base and prime editing can correct some forms of phenylketonuria (PKU) in mice and human cell lines, raising the prospect that this gene-editing approach could allow children born with the inherited metabolic disorder to have a treatment that would avoid the need for dietary restrictions and medication.
NGGT (Suzhou) Biotechnology Co. Ltd. has presented preclinical data on an AAV vector approach that expresses human PAH, rAAV8-PAH, also known as NGGT-002. NGGT-002 has liver tropism and it was codon-optimized for expressing PAH in the liver.
With PTC Therapeutics Inc.’s positive results in phase III with sepiapterin for pediatric and adult patients with phenylketonuria (PKU), attention turned to the would-be showdown with Kuvan (sapropterin dihydrochloride), the drug from Biomarin Pharmaceuticals Inc. that was approved in December 2017.
Phenylketonuria (PKU) is an autosomal recessive disorder where the primary catabolic pathway for phenylalanine (Phe) is disrupted due to mutations in the gene encoding PAH. Elevated Phe levels lie behind several neuropathologic anomalies that can lead to severe and irreversible mental retardation, if untreated.
Momentum is building at Jnana Therapeutics Inc. The firm has raised $107 million in a series C round and banked another $50 million up front from a new drug discovery and development pact with Roche Holding AG, which could potentially deliver significant near-term milestones and more than $2 billion in future milestone payments. It also commenced recruitment onto a first-in-human study of its lead drug candidate, JNT-517, an inhibitor of the phenylalanine transporter SLC6A19, which is in development for phenylketonuria.
The FDA has put a hold on a clinical study of a rare disease gene therapy BMN-307 from Biomarin Pharmaceutical Inc. after several mice developed liver tumors following a high dose in a preclinical trial.
Jnana Therapeutics Inc. closed a $50 million series B round and took the covers off its lead program, a small-molecule inhibitor of the solute carrier transporter SLC6A19, which it is prepping for clinical trials in phenylketonuria (PKU).
Sometimes highly impactful serendipitous discoveries are made when performing genetic loss-of-function studies that were initially focused on putative tumor suppressors or other hypotheses.
