生まれつきの難聴の多くは遺伝子の変異が原因とされ、特に「GJB2」と呼ばれる遺伝子の異常が世界的に最も多く見られる。これまで根本的に治療する方法はなかったが、…

Chai and colleagues demonstrated that co-injection of AAV1 and AAV-ie carrying exogenous Gjb2 driven by a specific promoter effectively restored hearing in Gjb2-deficient mice. This combined AAV system could transduce the cochleae of large animals, did not impair hearing, and showed negligible systemic toxicity, indicating the system's efficiency and safety.

Skylark Bio dosed the first patient in a phase 1/2 trial of SKY-GJB2, a gene therapy for the most common form of genetic deafness in children.

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The GJB2 gene provides instructions for making a protein called gap junction beta 2, more commonly known as connexin 26. Learn about this gene and related health conditions.

Mutations in the GJB2 gene, which encodes Connexin 26 (Cx26), are responsible for the majority of cases of non-syndromic congenital hearing loss in humans. While murine GJB2 knockout models have provided mechanistic insight, anatomical and physiological differences limit their translational relevance. Pigs represent a valuable large-animal model because their auditory anatomy and maturation closely resemble those of humans. This study compared two genome-editing approaches to disrupt GJB2 in porcine oocytes before fertilization: (1) electroporation with CRISPR/Cas9 ribonucleoprotein and (2) microinjection with cytosine base editor (BE3) and single-guide RNAs (sgRNAs). Electroporation produced high mutation rates (70–90%) across three concentrations of Cas9/sgRNA but yielded mostly heterozygous or mosaic blastocysts, with limited homozygous knockouts (< 4%). BE3 achieved precise cytosine-to-thymine conversions that introduced premature stop codons, reaching up to 47% total editing and 20% homozygous nonsense alleles. However, blastocyst formation declined at higher component concentrations. Overall, BE3 produced more predictable mutations than conventional CRISPR/Cas9, although embryo developmental competence was dose-dependent. Both methods effectively targeted GJB2 and demonstrated feasibility of pre-fertilization genome editing in porcine oocytes. These findings establish the groundwork for generating GJB2-deficient pigs as translational models of Cx26-related congenital deafness and for future evaluation of gene-therapy strategies in a large-animal system.

We are proud to announce that 𝘁𝗵𝗲 𝗳𝗶𝗿𝘀𝘁 𝗽𝗮𝘁𝗶𝗲𝗻𝘁 𝗵𝗮𝘀 𝗯𝗲𝗲𝗻 𝗱𝗼𝘀𝗲𝗱 𝗶𝗻 𝘁𝗵𝗲 𝗦𝗢𝗡𝗜𝗫 𝗣𝗵𝗮𝘀𝗲 𝟭/𝟮 𝘁𝗿𝗶𝗮𝗹 𝗼𝗳 𝗦𝗞𝗬-𝗚𝗝𝗕𝟮. This important milestone advances the development of a potential one-time gene therapy for chi...

Investigadores japoneses corrigen la sordera genética causada por GJB2 usando edición de bases en un vector AAV de una sola dosis.

Noninvasive prenatal diagnosis (NIPD) for autosomal recessive nonsyndromic hearing loss (ARNSHL) has been rarely reported until recent years. Additionally, the existing method can not be used for chal...

R75W mutation in the gap junction β2 (GJB2) gene causes severe fragmentation of gap junction plaques, connecting adjacent cells and leading to syndromic hearing loss. In a new experimental study,...

Studying epigenetic changes in cancer development can reveal the role of tumor suppressor genes and their regulation by DNA methylation.

Congenital hearing loss refers to impaired auditory function that occurs due to genetic causes. GJB2 is the gene responsible for approximately half of all cases of hereditary hearing loss.

Abstract Infertility mostly affects more than one member in a family, increasing the chances that the underlying cause is genetic. WGS aids in the discovery of novel variations through a variety of processes that cause infertility. To identify potential infertility-causing variations using WGS, a comprehensive method for analyzing the entire genome, and to identify the underlying mechanisms that may be targeted for future disease management. For this purpose, we identified a family with two male members exhibiting clinically diagnosed infertility and one fertile member. Blood samples were collected and subjected to WGS for CNV, SNV, and Run of homozygosity (ROH) analysis. The resulting WGS data were analyzed using bioinformatics tools/pipelines to investigate potential variants. We identified missense and stop-gain variations in TUBA3C and GJB2 genes as probable causes of Deafness Infertility Syndrome. Importantly, the TUBA3C variant represents the third deleterious variant linked to a

France's ANSM has authorized the Phase I/II HearConnex clinical trial of Sensorion's SENS-601, with patient dosing targeted for early 2027.

BACKGROUND AND PURPOSE: Although effects of deafness on the brain have been reported, little is known about the differential impact of genetic versus acquired etiologies. Our purpose was to assess cortical volumetric differences and hemispheric asymmetry in children with gap junction protein beta-2 (GJB2)- and congenital cytomegalovirus (cCMV)-related hearing loss compared with age- and sex-matched controls. MATERIALS AND METHODS: In this retrospective study, 3D T1-weighted sequences of children with cCMV-related hearing loss, GJB2-related hearing loss, and normal hearing were analyzed using FreeSurfer volumetric segmentation. Cortical volumes of Heschl gyrus (HG), planum polare (PP), planum temporale (PT), lateral aspect of superior temporal gyrus (LSTG), primary visual cortex, and cuneus were assessed. We performed a linear mixed model analysis to investigate cortical volumetric differences between 1:3 case:control-matched groups, adjusting for age, sex, and field strength. The laterality index was calculated to assess hemispheric asymmetry, and a 2-tailed 1-sample t test was used to compare the distribution of values against zero. Statistical significance was determined at a threshold of P < .05. RESULTS: Twenty-two children with cCMV-related hearing loss, 7 children with GJB2-related hearing loss, and 87 age- and sex-matched children with normal hearing were included. Significant differences were observed between the cortical volumes in the right ( P = .03), left ( P = .03), and total cuneus ( P = .02) between GJB2-related hearing loss and controls; HG ( P = .02) and PT ( P < .001) on the right; LSTG ( P = .002) on the left; and the total HG ( P = .02) and PT ( P < .001) between cCMV-related hearing loss and controls. HG was significantly larger on the left in GJB2-related SNHL ( P = .01), and the HG, PT, and LSTG were significantly larger on the left with a significantly larger right cuneus in both cCMV-related hearing loss and controls ( P < .01). CONCLUSIONS: GJB2-related hearing loss is associated with volumetric alterations in the visual cortices, and alterations in the auditory cortical regions occur in cCMV-related hearing loss. Particular auditory areas showed significant leftward asymmetry in GJB2- and cCMV-related hearing loss and controls. In contrast, the visual areas showed significant rightward asymmetry in both CMV-related hearing loss and controls. cCMV : congenital cytomegalovirus CMV : cytomegalovirus GJB2 : gap junction protein beta-2 HG : Heschl gyrus IQR : interquartile range LI : laterality index LSTG : lateral aspect of superior temporal gyrus PP : planum polare PT : planum temporale pvc : primary visual cortex SNHL : sensorineural hearing loss

Skylark Bio dosed the first patient in a phase 1/2 trial of SKY-GJB2, a gene therapy for the most common form of genetic deafness in children.