Genetic/congenital

ONYX-101 restores COL4A5 expression in X-linked Alport syndrome

Wed, 27 May 2026 09:00:00 -0400

X-linked Alport syndrome is an inherited kidney disease caused by pathogenic mutations in the COL4A5 gene. Patients develop hematuria, proteinuria and kidney function decline leading to end-stage renal disease. Nionyx Bio Inc. has developed ONYX-101, a novel kidney-targeting therapeutic designed to ensure durable COL4A5 restoration through dual-vector AAV delivery using NYX capsids that were optimized for kidney targeting.

Addition Therapeutics presents approach for Fabry disease

Tue, 26 May 2026 09:00:00 -0400

Fabry disease is a lysosomal storage disease tied to the X chromosome and caused by pathogenic variants in the GLA gene encoding galactosidase A. It is characterized by progressive accumulation of galactosidase A substrates, including Gb3 and lyso-Gb3, mainly in the kidney, heart and nervous system.

Gemma Biotherapeutics’ GB-703 shows promise for DMD

Tue, 26 May 2026 09:00:00 -0400

AAV-based therapies for Duchenne muscular dystrophy (DMD) have shown efficacy, but have limitations such as poor delivery to target tissues and toxicity associated with the vector. Gemma Biotherapeutics Inc. has developed a gene therapy candidate, GB-703, which uses a new myotropic, integrin-binding AAV capsid containing a codon-optimized, deimmunized hybrid payload.

Unmasking the X: EPAC2 shifts the fragile X landscape

Thu, 21 May 2026 09:00:00 -0400

Researchers at UCLA have shown that divergent neuronal signaling in fragile X mice converges on EPAC2, a druggable target whose inhibition restores circuit activity and alleviates core behavioral impairments.

HSPCs delivering tissue-penetrating frataxin ameliorate Friedreich’s ataxia symptoms

Wed, 20 May 2026 09:00:00 -0400

Researchers at the University of London and collaborating institutions have developed a gene and cell therapy approach that enables sustained systemic frataxin protein delivery, improving motor performance and tissue pathology, and supporting a promising translational strategy for long-term disease stabilization in Friedreich’s ataxia patients.

‘Detargeted’ targeted gene therapy improves activity in Pompe

Wed, 20 May 2026 09:00:00 -0400

A new strategy aims to improve gene therapy for Pompe disease by optimizing both the genetic component that restores the function of a deficient lysosomal enzyme and the vector that delivers it to the target tissue while avoiding the liver. The findings suggest that combining an optimized transgene with a targeted capsid could significantly enhance the effectiveness of gene therapy for Pompe disease.

Biocryst’s BCX-17725 as new approach for Netherton syndrome

Tue, 19 May 2026 09:00:00 -0400

Netherton syndrome is a rare disease caused by loss of activity of the lympho-epithelial Kazal-type-related inhibitor (LEKTI) protein, which in turn is caused by mutations in its encoding gene, SPINK5. This deficiency leads to the triggering of the kallikrein (KLK) signaling cascade resulting in skin barrier dysfunction, inflammation and atopy. At the recent Society for Investigative Dermatology meeting, Biocryst Pharmaceuticals Inc. presented early data on BCX-17725, a KLK5/KLK14 inhibitor fusion protein developed to restore LEKTI functioning in patients with Netherton syndrome.

Korro Bio nominates new candidate for AATD

Tue, 19 May 2026 09:00:00 -0400

Korro Bio Inc. has announced the selection of KRRO-111 as a development candidate for the treatment of alpha-1 antitrypsin deficiency (AATD), a genetic disorder most commonly caused by a single missense mutation in SERPINA1.

ASGCT 2026: Directed evolution in gene therapy

Fri, 15 May 2026 09:00:00 -0400

Directed evolution has become a central pillar in gene therapy. This engineering strategy enables the generation of more efficient variants of genetic editors and delivery vectors. Molecular diversification methods are increasingly sophisticated and are now accelerated by machine learning and AI tools, as showcased at the 29th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) held in Boston this week.

ASGCT 2026: Uncovering the mechanisms of AAV toxicity

Thu, 14 May 2026 09:00:00 -0400

Gene therapies rely on vectors to reach the target tissue where they act, such as adeno-associated viruses (AAVs) or lipid nanoparticles (LNPs), among other delivery strategies. Each combination is optimized for a specific cell type and indication, aiming to overcome challenges such as efficacy, specificity and toxicity. On May 13, 2026, two sessions included in the scientific symposia of the 29th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT), being held in Boston this week, addressed AAV-related toxicities, which have led to fatal cases in clinical trials and remain an area for improvement in approved therapies.

ASGCT 2026: Circular RNA, the new beast in gene and cell therapy

Wed, 13 May 2026 09:00:00 -0400

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.

OPGx-BEST1 restores BEST1 expression in retinal cells

Tue, 12 May 2026 09:00:00 -0400

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.

JUV-161 reverses structural and functional muscle decline

Tue, 12 May 2026 09:00:00 -0400

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.

ASO therapy prevents hydrocephalus in a monogenic syndrome model

Mon, 11 May 2026 09:00:00 -0400

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

Engineered programmable inhibitory binders to target CRAC channelopathies

Thu, 07 May 2026 09:00:00 -0400

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 advances gene therapy for CDKL5 deﬁciency disorder

Wed, 06 May 2026 09:00:00 -0400

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.

AAV9-delivered AntagoNATs have preclinical efficacy as one-time treatment for Dravet syndrome

Mon, 04 May 2026 09:00:00 -0400

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.

A new prodrug approach overcomes trofinetide’s limitations

Wed, 29 Apr 2026 09:00:00 -0400

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.

Single-gene therapy for LSDs with modified lysosomal enzyme shows preclinical efficacy

Mon, 27 Apr 2026 09:00:00 -0400

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.

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.