Circular RNA (circRNA) is not a new concept, but it is a novel strategy in the field of gene and cell therapy. While mRNA vaccines have revolutionized medicine, this RNA fragment without free ends surpasses their performance in both efficacy and durability, bringing it to the attention of several pioneering companies. The latest advances in circRNA presented at the 29th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) clearly surpass the performance achieved with linear mRNA.

Researchers at Opus Genetics Inc. reported the efficacy of OPGx-BEST1, an AVV-based gene therapy developed to deliver a functional BEST1 transgene to retinal pigment epithelium (RPE) cells to re-establish normal BEST1 expression and activity.

At the European Congress of Endocrinology in Prague, researchers from Juvena Therapeutics Inc. presented the effects of JUV-161, a fusion protein consisting of human insulin-like growth factor 2 linked to human serum albumin, in preclinical models of myotonic dystrophy type 1 (DM1) and sarcopenia.

Researchers from McGill University and collaborating institutions aimed to investigate whether oligonucleotides are a viable drug class to prevent hydrocephalus.

CRAC channels are essential for immune and developmental processes, and dysregulation of store-operated Ca2+ entry (SOCE) has been implicated in several human diseases. Researchers from Texas A&M University and collaborators recently described the engineering of genetically encoded CRAC channel inhibitory binders (CRABs) derived from the ORAI C-terminal region, a defined STIM1-binding interface.

Elaaj Bio, a wholly owned subsidiary of the nonprofit Loulou Foundation, has entered into a partnership with Viralgen Vector Core SL to advance a gene therapy program for CDKL5 deficiency disorder.

Dravet syndrome is a rare, severe, lifelong developmental and epileptic encephalopathy that begins in infancy and is marked by prolonged, often fever-triggered seizures that are difficult to control. It is usually caused by mutations in the SCN1A gene and is associated with developmental delay, cognitive and behavioral impairment, and reduced life expectancy.

Rett syndrome (RTT) is a rare neurodevelopmental condition affecting multiple organ systems and is most often driven by mutations in the X-linked MECP2 gene. Researchers at Shanghai Duomirui Biological Technology Co. Ltd. have developed a new class of trofinetide prodrugs aimed at addressing limitations related to drug administration and pharmacokinetic properties.

In previous work, researchers from Kawasaki Medical School and collaborating institutions engineered a modified HEXB construct, modHexB, to improve GM2 ganglioside (GM2) recognition and GM2-activating protein (GM2A) interaction. The team has now combined these previous advancements to develop a new gene therapy strategy for Sandhoff disease.

A modified version of CRISPR-Cas9 has enabled, for the first time, the efficient integration of a large transgene capable of inactivating entire chromosomes into one of the three copies of chromosome 21 in Down syndrome-derived cells. The goal is to silence the extra copy to limit the gene-dosage imbalance that drives many features of trisomy 21. Researchers at Beth Israel Deaconess Medical Center turned to XIST, the long noncoding RNA responsible for the natural silencing of the X chromosome in females. Using this strategy, they achieved integration efficiencies of 20% to 40% and a partial reduction in the overexpression of chromosome 21 genes.