Cell therapy weekly: customized CRISPR gene therapy success
This week: an infant with a rare metabolic disorder was successfully treated with the world’s first personalized CRISPR gene-editing therapy, while Fractyl Health (MA, USA) submitted a Clinical Trial Application (CTA) for a one-time gene therapy for Type II diabetes. Plus, Latus Bio (PA, USA) identified a novel capsid as a promising vector for neurodegenerative disorders such as Parkinson’s disease.
The news highlights:
- Customized CRISPR gene therapy success
- Type II diabetes gene therapy progresses with CTA in Europe
- Discovery of a novel AAV capsid for neurodegenerative diseases
Customized CRISPR gene therapy success
At the American Society of Gene & Cell Therapy Annual Meeting in New Orleans (12–15 May 2025; LA, USA) the Children’s Hospital of Philadelphia and Penn Medicine (both PA, USA) presented a successful CRISPR gene editing treatment for an infant with severe carbamoyl phosphate synthetase 1 (CPS1) deficiency – a metabolic disorder. This rare genetic condition, caused by a faulty CPS1 gene, leads to toxic ammonia buildup. Typically, liver transplants are necessary, but the infant, days old at diagnosis, did not meet the age requirement for a transplant.
Researchers Rebbeca Ahrens-Nicklas, Kiran Musunuru and their team, developed a customized CRISPR therapy and used lipid nanoparticles to deliver the treatment to the liver, effectively correcting the faulty gene.
The infant received the first infusion in late February 2025, followed by doses in March and April 2025. The child, aged between six to seven months at first infusion, showed no serious side effects, tolerated increased dietary protein and recovered from common illnesses like rhinovirus without ammonia buildup.
“We want each and every patient to have the potential to experience the same results we saw in this first patient, and we hope that other academic investigators will replicate this method for many rare diseases and give many patients a fair shot at living a healthy life,” expressed Musunuru. “The promise of gene therapy that we’ve heard about for decades is coming to fruition and it’s going to utterly transform the way we approach medicine.”
The study was published in The New England Journal of Medicine.
Type II diabetes gene therapy progresses with CTA in Europe
Fractyl Health has submitted the first module of its CTA in Europe for RJVA-001, a one-time gene therapy designed to treat Type II diabetes and obesity.
The therapy aims to locally express glucagon-like peptide-1 (GLP-1) in pancreatic beta cells using nutrient-responsive control, potentially allowing for hormone secretion without the high circulating levels that may provoke side effects associated with systemic GLP-1 treatments, such as GLP-1 receptor agonists.
Clearance of the CTA will position the company to commence a Phase I/II study to evaluate the safety, tolerability and preliminary efficacy of RJVA-001. The trial will be an open-label, multicenter study in adults with poorly controlled Type II diabetes who have previously used multiple glucose-lowering agents.
“We’ve spent decades managing [Type II diabetes] as a chronic, progressive disease, and this upcoming first-in-human study of RJVA-001 represents the first real attempt to reverse it at the source by targeting the beta cell directly,” explained Jacques J.G.H.M. Bergman, Deputy Chair at Department of Gastroenterology and Hepatology at Amsterdam University Medical Center (Netherlands).
Discovery of a novel AAV capsid for neurodegenerative diseases
Latus Bio announced the discovery of a novel adeno-associated virus (AAV) capsid variant AAV-DB-3, which aims to improve delivery to deep brain structures impacted by neurodegenerative diseases.
“AAV-DB-3 represents a major step forward in solving one of the biggest challenges in both Huntington’s and Parkinson’s disease gene therapy — delivering genetic payloads precisely and effectively to deep brain structures,” remarked Jang-Ho Cha, Chief Scientific Officer at Latus.
AAV-BD-3 was selected from millions of potential candidates due to its promising capabilities to:
- Consistently transfer genes to a high percentage of neurons in critical brain regions
- Increase transgene mRNA expression in areas relevant to Huntington’s disease
- Potentially enhance neuronal transduction for clinical applications.
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