Genetic/congenital

CRISPR and XIST silence one chromosome 21 copy in Down syndrome

Mon, 20 Apr 2026 09:00:00 -0400

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.

Sex differences shape gene activity across the human brain

Fri, 17 Apr 2026 09:00:00 -0400

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 expands early-stage pipeline

Thu, 09 Apr 2026 09:00:00 -0400

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.

Topical ASO restores WRN function for chronic skin ulcers in Werner syndrome

Wed, 08 Apr 2026 09:00:00 -0400

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.

Alltrna’s AP-003 cleared for trials for stop codon disease

Wed, 01 Apr 2026 09:00:00 -0400

Alltrna has obtained approval in Australia to initiate a phase I trial of AP-003 in healthy volunteers under Australia’s TGA clinical trial notification scheme. AP-003 is a chemically modified, engineered transfer RNA (tRNA) oligonucleotide encapsulated in a clinically validated, liver-directed lipid nanoparticle.

CRISPR-mediated utrophin upregulation preclinically improves DMD

Wed, 01 Apr 2026 09:00:00 -0400

Currently available disease management options for Duchenne muscular dystrophy (DMD) are mostly symptomatic. Several strategies based on exon-skipping or gene transfer have been proposed to restore dystrophin expression, but can only address specific subsets of DMD patients and/or provide limited clinical benefits. Upregulating utrophin (UTRN), a structural and functional paralogue of dystrophin, has been proposed as an alternative therapeutic approach that may be suitable for all DMD patients, regardless of their genetic defect.

Antitumoral antibodies cross the BBB and alter brain signaling

Tue, 31 Mar 2026 09:00:00 -0400

Certain cancers, such as triple-negative breast cancer, produce antibodies that, although they help fight the tumor, can cross the blood-brain barrier and alter the function of NMDA receptors (NMDAR) in the brain, which are essential for neuronal signaling. Scientists at Cold Spring Harbor Laboratory (CSHL) have identified their origin and described how this process is linked to the maturation of these antibodies, which can activate or inhibit the receptor, causing neurological and psychiatric symptoms.

Molecular signatures show subtypes in neurodegenerative diseases

Mon, 30 Mar 2026 09:00:00 -0400

Parkinson’s disease is a progressive neurodegenerative disorder best known for its motor symptoms. However, a proportion of patients also develop dementia as the condition advances. Yet the biological divide between those who experience this cognitive decline and those who do not has remained an open question. Are they different conditions or simply stages of the same disease?

Efficient editing in skeletal muscle of dystrophic mice with SORT LNPs encapsulating Cas9 mRNA

Wed, 25 Mar 2026 09:00:00 -0400

Gene editing holds promise for treating neuromuscular disorders such as limb-girdle muscular dystrophy, but its clinical translation remains challenging due to a lack of complementary delivery tools for the extensive network of skeletal muscles in the human body. A team at University of Massachusetts Chan Medical School compared editing outcomes mediated by either Cas9 mRNA and RNP delivery to skeletal muscle via local injection in the context of the previously described selective organ targeting (SORT) lipid nanoparticles (LNPs) platform.

Discovery and characterization of Arthex Biotech’s ATX-01 for myotonic dystrophy type 1

Mon, 23 Mar 2026 09:00:00 -0400

Researchers from Arthex Biotech SL, the University of Valencia (Spain) and collaborators sought to address the lack of optimized microRNA (miRNA)-targeting antisense oligonucleotides (anti-miRs) for upregulating MBNL1 in myotonic dystrophy.

ADPD 2026: Three inflection points to target Alzheimer’s disease

Fri, 20 Mar 2026 09:00:00 -0400

A new way of understanding Alzheimer’s disease, based on biological inflection points that mark decisive moments in the progression of the disorder, could change how new drugs are developed to achieve more effective therapies. This new perspective could rethink strategies that depend not so much on the target itself, but on the precise moment at which it is addressed.

PTBP1 identified as potential target for Duchenne muscular dystrophy

Thu, 19 Mar 2026 09:00:00 -0400

Researchers from the China Pharmaceutical University and Guangdong Pharmaceutical University (China) have unveiled the crucial role of the alternative splicing of E2A in myogenic progression and demonstrated that PTBP1, by controlling E2A alternative splicing, is a critical regulator of myogenesis.

ADPD 2026: Three inflection points to target Alzheimer’s disease

Thu, 19 Mar 2026 09:00:00 -0400

ENTR-601-51 confers muscle function recovery in DMD

Wed, 18 Mar 2026 09:00:00 -0400

Exon skipping therapies based on antisense phosphorodiamidate morpholino oligomer (PMO) have great potential to restore dystrophin in the skeletal muscle and treat Duchenne muscular dystrophy (DMD). Entrada Therapeutics Inc. has developed an endosomal escape vehicle conjugated to DMD exon skipping PMOs (exon 51 skipping), ENTR-601-51, for the potential treatment of DMD.

ADPD 2026: Can we prevent dementia? Scientists quantify it

Wed, 18 Mar 2026 09:00:00 -0400

Neurodegenerative disease and cognitive decline cannot be explained by a single process. Beta-amyloid plaques, hyperphosphorylated tau, alpha-synuclein, activated microglia and astrocytes, altered receptors such as TREM2, mitochondrial dysfunction, epigenetic changes and cerebrovascular alterations all seem to contribute to the development of dementia in Alzheimer’s disease (AD). While scientists attempt to address each of these elements, prevention is growing as a primary goal.

SFL-0821 shows promise for facioscapulohumeral muscular dystrophy

Tue, 17 Mar 2026 09:00:00 -0400

Facioscapulohumeral muscular dystrophy (FSHD) is a muscle wasting disease caused by aberrant expression of double homeobox protein 4 (DUX4). When DUX4 is activated in skeletal muscle, it triggers myocyte cell death after several transcriptional changes, thus genetic DUX4 silencing arises as a promising approach for treating FHSD.

Digital model simulates the first fully functioning living cell

Mon, 16 Mar 2026 09:00:00 -0400

Entering a cell and watching its entire inner machinery at work, how DNA is copied, how proteins are assembled, or how it splits in two, has been, for decades, an impossible dream. Now, scientists at the University of Illinois have recreated everything that happens inside a cell at molecular scale in an unprecedented computational model. Syn3A is the first 4D digital cell, capable of combining time and space to simultaneously represent all the internal processes that drive the life cycle of a minimal prokaryotic organism.

First-in-class POLG activator restores mtDNA across mutations

Fri, 13 Mar 2026 09:00:00 -0400

Researchers from Pretzel Therapeutics Inc. presented preclinical data of PX-578, a first-in-class POLG activator aimed at restoring mtDNA replication and mitochondrial function independently of mitochondrial DNA depletion syndromes genotype.

Chemicare’s CIC-39 shows promise for DMD treatment

Fri, 13 Mar 2026 09:00:00 -0400

Researchers from Chemicare Srl and the University of Piemonte Orientale have presented preclinical results regarding their (SOCE) negative regulator CIC-39. Researchers evaluated the dysregulation of SOCE in both ex vivo and in vivo models of Duchenne muscular dystrophy (DMD), as well as evaluated the therapeutic potential of CIC-39 in DMD.

Lentiviral HSC gene therapy shows preclinical efficacy for GM1 gangliosidosis treatment

Thu, 12 Mar 2026 09:00:00 -0400

GM1 gangliosidosis is a lysosomal storage disease caused by mutations in the human GLB1 gene, encoding the ubiquitous lysosomal β-galactosidase. GM1 causes a rapidly progressing neurodegeneration, which can be lethal in the first 2 years of life in the most severe cases.

AAV-based gene therapy for GBA1-related diseases, including Parkinson’s and Gaucher

Thu, 12 Mar 2026 09:00:00 -0400

Glucocerebrosidase (GCase), encoded by the gene GBA1, is a ubiquitous lysosomal enzyme that breaks down lipid substrates, glucosylceramide (GL-1) and glucosylsphingosine (Lyso-GL1), into glucose and ceramide. Loss-of-function mutations in GBA1 reduce GCase activity, resulting in lipid accumulation within lysosomes and subsequent lysosomal dysfunction.

SGT-212 restores FXN function in Friedreich’s ataxia models

Wed, 11 Mar 2026 09:00:00 -0400

Friedreich’s ataxia (FA) is an inherited neurodegenerative disorder caused by GAA repeat expansions in the FXN gene, which produces a mitochondrial protein vital for iron-sulfur cluster assembly and energy metabolism. Researchers at Solid Biosciences Inc. presented preclinical data supporting the first-in-human trial on SGT-212 gene therapy in FA models.

Alternative splicing strategy shows promise for Rett syndrome

Wed, 04 Mar 2026 07:00:00 -0500

A therapeutic strategy based on alternative splicing of the MECP2 gene could restore protein levels in Rett syndrome, a neurological disorder caused by mutations in that gene. Scientists at Baylor College of Medicine have successfully tested this approach both in vitro in neurons from Rett patients that produce some functional protein, correcting the altered gene expression and improving neuronal functions, and in vivo in mice.

Beam Therapeutics reveals new program for PKU

Fri, 27 Feb 2026 08:00:00 -0500

Beam Therapeutics Inc. has added a new program to its liver-targeted genetic disease franchise, BEAM-304, for the treatment of phenylketonuria (PKU).

Brain-targeted AAV gene therapy shows promise for CLN5 disease in mice

Thu, 19 Feb 2026 08:00:00 -0500

Researchers from University College London and collaborating institutions have recently published results from their study aiming to optimize gene therapy for CLN5 disease.

Inventisbio discovers PI3Kα mutant inhibitors

Tue, 17 Feb 2026 08:00:00 -0500

Inventisbio Co. Ltd. and Inventisbio LLC have divulged compounds acting as phosphatidylinositol 3-kinase α (PI3Kα) E545K mutant inhibitors.

Anti-tFR1 nanobody-I2S gene therapy corrects Hunter syndrome neuropathy in mice

Tue, 17 Feb 2026 08:00:00 -0500

Hunter syndrome, also called mucopolysaccharidosis II, is an X-linked genetic lysosomal disorder caused by loss-of-function mutations in the IDS gene, encoding iduronate-2-sulfatase (I2S). I2S is a lysosomal enzyme responsible for the cleavage of glycosaminoglycans (GAGs), and its deficiency results in accumulation of GAGs leading to a multisystemic disorder.

New models, gene therapy approach for ocular phenotype of Friedreich’s ataxia

Thu, 12 Feb 2026 08:00:00 -0500

Friedreich’s ataxia (FA), the most common form of hereditary ataxia, is an autosomal recessive neurodegenerative disorder affecting multiple organ systems, and causing cardiomyopathy, scoliosis, muscle weakness, speech impairment and other systemic issues.

Tangram’s TGM-148 demonstrates pan-bleeding disorder therapeutic potential

Fri, 06 Feb 2026 08:00:00 -0500

Researchers at Tangram Therapeutics Inc. have presented preclinical safety and efficacy data for TGM-148 in a model of von Willebrand disease.

Study uncovers pathogenic variants of Lynch syndrome

Wed, 21 Jan 2026 08:00:00 -0500

A new method, based on gene editing with oligonucleotides and functional analyses, identifies which variants of DNA repair genes associated with Lynch syndrome are truly harmful and which are not. Scientists at The Netherlands Cancer Institute have developed this technique and classified these gene variants in both coding and noncoding regions, distinguishing those that are pathogenic from those that are benign.