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.

Genes that are switched on or off in the human brain differ between men and women. Moreover, these differences are not uniform. They vary across cortical regions and cell types. Scientists at the National Institute of Mental Health (NIMH) and the National Institute on Aging (NIA) used single-cell sequencing and unveiled distinct gene expression patterns regulated by hormones and sex chromosomes. This detailed map of the brain’s molecular biology shows how women and men switch on and off more than 3,000 brain genes differently and expands the catalogue of X chromosome genes that escape inactivation.

Proqr Therapeutics NV has highlighted the continued progression and expansion of its early-stage pipeline of RNA editing therapies, including programs in cholestatic diseases, Hurler syndrome, metabolic dysfunction-associated steatohepatitis and Rett syndrome.

Werner syndrome results from biallelic mutations in the WRN gene on chromosome 8, leading to accelerated aging symptoms. Researchers at Sumitomo Pharma Co. Ltd. have reported the development and characterization of WRN-108, a splice-switching antisense oligonucleotide (ASO) designed to induce exon 27 skipping in WRN transcripts carrying the c.3139-1G>C mutation.