Life Edit® Therapeutics Inc., an ElevateBio® company focused on next-generation gene editing technologies and therapeutics, today announced the presentation of the first preclinical data from the company’s Huntington’s disease program across three presentations at CHDI’s 18th Annual Huntington’s Disease Therapeutics Conference taking place April 24-27, 2023, in Dubrovnik, Croatia.
“Next-generation gene editing capabilities are central to our ecosystem as we power the cell and gene therapy industry”
Life Edit’s presentations underscore the ability of its gene editing platform to selectively target disease-associated genetic factors to treat life-threatening diseases. Huntington’s disease is an inherited neurodegenerative disorder caused by a mutation in the huntingtin gene as a result of a cytosine-adenine-guanine (CAG) trinucleotide expansion. This results in a mutant form of the huntingtin protein (mutHTT) that damages brain cells. Wild-type HTT protein is purported to be physiologically critical, hence selective editing of the mutant HTT (mutHTT) protein is necessary for therapeutic benefit.
Life Edit has generated new, small RGNs with expanded protospacer adjacent motif (PAM) diversity that can separately target both the T and C alleles of an exonic SNP in the HTT gene. The small size of Life Edit’s nucleases also enabled packaging and delivering in a single AAV vector. Life Edit evaluated preclinical development candidates in clinically relevant YAC128 and BACHD transgenic murine disease models that contain a full-length human mutant HTT gene. AAV5-delivered Life Edit gene editing systems enabling allele-specific targeting of mutant HTT demonstrated dose-response reductions in striatal mutHTT protein with clinically meaningful reductions of >50% observed. Dose-dependent increases in insertions and deletions (INDELs) correlated with reductions in mutHTT levels. High vector copy numbers were detected in the striatum and cortex up to 12-weeks post injection (furthest time point tested). These results support continued evaluation and identification of a development candidate.
“These exciting preclinical data underscore the enormous therapeutic potential of our gene editing systems to deliver a life-transforming therapy for patients suffering from Huntington’s disease, a debilitating genetic disease with no approved therapies,” said Mitchell Finer, Ph.D., Chief Executive Officer, Life Edit Therapeutics, and President, R&D, ElevateBio. “The PAM diversity of Life Edit’s proprietary RNA-guided nucleases allows us to target virtually any genomic site, including those enabling editing of both T and C SNP alleles as demonstrated in these data. Our mission to make any edit, anywhere possible can transform how we approach new treatments for the most challenging genetic disorders.”
CHDI Presentation Details
Date and Time: Tuesday, April 25, 2023: 11:55 a.m. – 12:20 p.m. CEST
Session 1: DNA Structure-Function of mHTT: Pathogenesis and Opportunities for Intervention
Presentation Title: Allele-selective SNP editing utilizing AAV5-delivered Life Edit nuclease and guide RNA resulting in meaningful reduction of mutant HTT protein
Date and Time: Wednesday, April 26, 2023; 1:00 p.m. – 2:30 p.m. CEST
Poster #16: Group A: Huntingtin Lowering
Poster Title: Allele selective SNP editing utilizing AAV5-delivered Life Edit nuclease and guide RNA resulting in meaningful reduction of mutant HTT protein
Date and Time: Wednesday, April 26, 2023; 1:00 p.m. – 2:30 p.m. CEST
Poster #26: Group A: Huntingtin Detection/Quantification
Poster Title: Mutant and wildtype huntingtin protein quantitation utilizing automated capillary electrophoresis
Advancements to the Life Edit Platform
Life Edit’s gene editing platform offers a large and diverse library of RNA-guided nucleases (RGNs), base editors, and reverse transcriptase editors, making it one of the most flexible gene editing technology platforms available. The RGNs are smaller in size when compared to conventional nucleases, potentially enabling greater versatility for delivery. Life Edit’s nuclease collection features a range of Protospacer Adjacent Motifs (PAMs), short sequences that determine the DNA segments in the genome to which a nuclease can bind. The diversity of Life Edit’s PAM collection offers unprecedented access to the genome to treat and cure genetic diseases.
The platform has achieved several key milestones over the past year, including the generation of new base editors and RNA-guided nucleases with expanded PAM diversity towards making any edit, anywhere possible. Additionally, the platform has demonstrated multiplex base editing of up to five genes, simultaneous knock-in/knock-out in primary T-cells, and in vivo editing in the liver and brain.
“Next-generation gene editing capabilities are central to our ecosystem as we power the cell and gene therapy industry,” said David Hallal, Chairman and Chief Executive Officer of ElevateBio. “Our partners recognize the immense value of our library of novel genome editing systems and its potential to enable them to develop a broad array of advanced therapies. Our recent technology advancements will help us to further power the Life Edit gene editing platform, support our partners, and selectively build out our pipeline of innovative therapeutic candidates.
Source: https://www.businesswire.com/
