Otoferlin is a calcium sensor protein critical for the transmission of the signal from inner hair cells (IHCs) to the spiral ganglion neurons (SGNs), and it is encoded by the OTOF gene. Pathogenic biallelic loss of function variations in OTOF result in failure of synaptic transmission, causing autosomal recessive deafness 9 (DFNB9), which is a congenital severe-to-profound auditory neuropathy.

By applying deep learning methods to a large database of zinc finger nucleases, researchers at the University of Toronto and New York University have developed an algorithm, Zfdesign, that was able to design custom zinc fingers for any given stretch of DNA. “I think this system levels the playing field for zinc fingers and CRISPR,” said Philip Kim, co-corresponding author of the team's paper published online in Nature Biotechnology on Jan. 26, 2023.

Herophilus Inc. is conducting in vivo studies of lead candidate HRP-12975, a small-molecule therapy for Rett syndrome, with funding from the Rett Syndrome Research Trust. The company is generating efficacy and safety data with HRP-12975 using genetic mouse models of Rett syndrome.

Decibel Therapeutics Inc. has received clearance of its clinical trial application (CTA) by the U.K.'s Medicines and Healthcare products Regulatory Agency (MHRA) to initiate a phase I/II trial of gene therapy DB-OTO in pediatric patients with congenital hearing loss due to an otoferlin deficiency.

Exegenesis Bio (Hangzhou Exegenesis Biotechnology Co. Ltd.) has received FDA clearance of its IND application for EXG-102-031, a recombinant adeno-associated virus (rAAV)-based gene therapy that is being studied for the treatment of neovascular age-related macular degeneration (AMD).

Rocket Pharmaceuticals Inc. has added RP-A601 to its cardiac gene therapy portfolio for the treatment of arrhythmogenic cardiomyopathy due to plakophilin 2 pathogenic variants (PKP2-ACM).

CRISPR gene editing has been one of the important advances of the last decade, in biotechnology and increasingly in medicine. First applied to human cells in 2013, and honored with the 2020 Nobel Prize in Physiology or Medicine, its meteoric rise can make CRISPR look like the molecular equivalent of a miracle healer. But in the research and clinical trenches, CRISPR-based approaches, like any others, need to find applications where their desired effects outweigh their side effects. And finding those applications necessitates ways to identify off-target effects.

Neurophth Therapeutics Inc. has received FDA clearance of its IND application for the in vivo gene replacement therapy NFS-02, a novel recombinant adeno-associated viral serotype 2 vector (rAAV2) containing a codon-optimized NADH-dehydrogenase subunit 1 (ND1) gene, for the treatment of Leber hereditary optic neuropathy (LHON) associated with ND1 mutation.

Eikonoklastes Therapeutics Inc. and Forge Biologics Inc. have established a manufacturing partnership to advance Eikonoklastes' adeno-associated viral (AAV)-based gene therapy, ET-101, into clinical trials for the treatment of patients with amyotrophic lateral sclerosis (ALS).