69 Small‑Molecule–regulated RNA switch achieves therapeutically safe levels of Frataxin in mouse models of Friedreich’s Ataxia

2026 Annual Meeting of the American Society of Gene and Cell Therapy: ASGCT 2026 Annual Meeting Abstracts. Available online 8 May 2026, Version of Record 8 May 2026. 

 69 Small‑Molecule–regulated RNA switch achieves therapeutically safe levels of Frataxin in mouse models of Friedreich’s Ataxia. 69 Small‑Molecule–regulated RNA switch achieves therapeutically safe levels of Frataxin in mouse models of Friedreich’s Ataxia. Jon Dempersmier, Mariam Elhawary, Ian McLachlan, Hayley Ulloa, Kai Li, Diane Hamann, Zhiping Weng, Ricardo Mouro Pinto, Travis Wager, Simon Xi, Sam Hasson; 

Friedreich’s ataxia (FA) represents a compelling use case for regulated gene therapy. FA is an autosomal recessive disorder caused by repeat expansion–mediated silencing of the FXN gene, resulting in impaired iron–sulfur cluster biogenesis, mitochondrial dysfunction, neurodegeneration, and cardiomyopathy. While constitutive AAV-mediated FXN replacement has shown efficacy in preclinical models, excessive Frataxin expression has been associated with cardiotoxicity, highlighting the need for controlled dosing.

This system consists of DNA-encoded regulatory elements, termed RSwitches, which are selectively modulated by matched synthetic small molecules, or RDrugs, in a dose-dependent manner. RDrugs direct specific pre-mRNA splicing events required for productive transgene expression, enabling temporal control on the order of hours and quantitative control of protein output almost five orders of magnitude from AAV vectors.

62 Development and Translation of PPL-001, an autologous, gene-edited CD34+ hematopoietic stem cell Therapy for Friedreich’s Ataxia

2026 Annual Meeting of the American Society of Gene and Cell Therapy: ASGCT 2026 Annual Meeting Abstracts. Available online 8 May 2026, Version of Record 8 May 2026.  62 

Development and Translation of PPL-001, an autologous, gene-edited CD34+ hematopoietic stem cell Therapy for Friedreich’s Ataxia  Anusha Sivakumar, Colin Exline, Stephanie Cherqui.

 Here, we present a GMP-compliant, commercially/clinically scalable manufacturing process and safety data of PPL-001, aimed at initiating the first-in-human HSPC and genome editing clinical trial for FRDA. 

These promising results of scale-up feasibility and safety support our efforts in clinical translation of CRISPR/Cas9 gene edited CD34+ HSPCs as a novel treatment approach for Friedreich’s ataxia.