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Antisense oligonucleotide therapeutic approach for Timothy syndrome

Timothy syndrome (TS) is a severe, multisystem disorder characterized by autism, epilepsy, long-QT syndrome and other neuropsychiatric conditions1. TS type 1 (TS1) is caused by a gain-of-function variant in the alternatively spliced and developmentally enriched CACNA1C exon 8A, as opposed to its counterpart exon 8. We previously uncovered several phenotypes in neurons derived from patients with TS1, including delayed channel inactivation, prolonged depolarization-induced calcium rise, impaired interneuron migration, activity-dependent dendrite retraction and an unanticipated persistent expression of exon 8A2–6. We reasoned that switching CACNA1C exon utilization from 8A to 8 would represent a potential therapeutic strategy. Here we developed antisense oligonucleotides (ASOs) to effectively decrease the inclusion of exon 8A in human cells both in vitro and, following transplantation, in vivo. We discovered that the ASO-mediated switch from exon 8A to 8 robustly rescued defects in patient-derived cortical organoids and migration in forebrain assembloids. Leveraging a transplantation platform previously developed7, we found that a single intrathecal ASO administration rescued calcium changes and in vivo dendrite retraction of patient neurons, suggesting that suppression of CACNA1C exon 8A expression is a potential treatment for TS1. Broadly, these experiments illustrate how a multilevel, in vivo and in vitro stem cell model-based approach can identify strategies to reverse disease-relevant neural pathophysiology. Antisense oligonucleotides effectively decrease the inclusion of exon 8A of CACNA1C in human cells both in vitro and in rodents transplanted with human brain organoids, and a single intrathecal administration rescued both calcium changes and in vivo dendrite morphology of patient neurons.

Fiji , Leica-stellaris , Teledyne-lumenera , Mount-polysciences , Leica-microsystems , Takara-bio , Beckman-coulter , Perkinelmer , International-electric-company , Fisher-scientific , Stanford-university , Bruker-corp

DNases, Ligases, and RNA Polymerases Market expected to Witness Huge Revenue Growth to 2031

DNases, Ligases, and RNA Polymerases Market expected to Witness Huge Revenue Growth to 2031
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France , South-africa , Germany , Mexico , Canada , Brazil , United-states , United-kingdom , South-korea , Argentina , Linac , Midi-pyrées

Middle East Stem Cell (Adult, Human Embryonic) Market

Dublin, April 10, 2024 (GLOBE NEWSWIRE) -- The

Dublin , Ireland , Abu-dhabi , Abuz-aby , United-arab-emirates , Saudi-arabia , Takara-bio , Cellgenix-gmb , Merck-kga , Abu-dhabi-stem-cells-center , Rising-funds-for-accelerating-stem-cell-research , Merck-kgaa

Platform Processes May Reduce AAV Gene Therapy Costs

Platform Processes May Reduce AAV Gene Therapy Costs
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James-cody , Clive-glover , Michael-haugwitz , Xuan-liu , Mathieu-boxus , Takara-bio , Thermo-fisher , National-institute-of-standards , Novartis , Sarepta-therapeutics , Biomarin-pharmaceutical , Spark-therapeutics

Takara Bio transforms single-cell landscape with new large-scale NGS profiling system for oncology biomarker discovery

Takara Bio transforms single-cell landscape with new large-scale NGS profiling system for oncology biomarker discovery
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United-states , American , Takara-bio , Carol-lou , Liz-quinn , Association-of-biomolecular-resource-facilities , Takara-bio-united-states-inc , Takara-bio-inc , American-association-for-cancer-research , Bio-united-states , Single-cell-system , Takara-bio-united-states

Nucleic Acid Sample Preparation Market Global and Regional Analysis 2023-2033: Increasing Demand for Reliable Next-Generation Sequencing (NGS) Platforms in Clinical Laboratories

/PRNewswire/ -- The "Nucleic Acid Sample Preparation Market - A Global and Regional Analysis: Focus on Technology, Application, Product, End User, and Country...

Dublin , Ireland , Canada , China , United-states , Japan , America , Chinese , Norgen-biotek , Omega-bio-tek , Takara-bio , Laura-wood

Global Immunoprecipitation Testing Market Industry Trends & 10 Year Growth Forecasts 2019-2029

/PRNewswire/ -- The "Global Immunoprecipitation Testing - Market Share Analysis, Industry Trends & Statistics, Growth Forecasts 2019 - 2029" report has been...

Dublin , Ireland , United-states , America , Takara-bio , Co-immunoprecipitation , Rockland-immunochemicals , Laura-wood , Genscript-biotech-corporation , National-human-genome-research-institute , Geno-technology , Biologics-international-corp

Digital PCR (DPCR) Market Set to Reach USD 2196.40 Million by 2030

Digital PCR (DPCR) Market Shows Exponential Growth by Revolutionizing molecular diagnostics through digital PCR technology

United-states , India , China , Russia , America , Takara-bio , Becton-dikinson , Asia-pacific , Software-and-services , Elitech-group , Abbott-laboratories , Enzo-life-sciences-inc

Asia-Pacific Gene Editing Technology Analysis Report 2024: Market to Reach $5.05 Billion by 2032 from $490 Million in 2023, Driven by Increasing Demand for Personalized Medicine

/PRNewswire/ -- The "Asia-Pacific Gene Editing Technologies Market: Analysis and Forecast, 2023-2032" report has been added to ResearchAndMarkets.com's...

China , South-korea , Dublin , Ireland , Australia , Singapore , India , Japan , Laura-wood , Research-methodology , Financial-health-of-the-company , Takara-bio-inc

Clinical Oncology Next-generation Sequencing Market Aims for US$ 1.14 Billion Valuation by 2029

Clinical Oncology Next-generation Sequencing MarketThe clinical oncology next-generation sequencing market share is expected to reach a value of US$ 449.4 million by 2022. Owing to the increasing application of next-generation sequencing (NGS) in clinical oncology for more effective, individualised cancer treatment,...

United-states , New-york , Delaware , California , America , Pacific-biosciences , Companies-hold , Greater-new-york-chamber , Takara-bio-inc , Consumer-technology , Market-insights-inc , Agilent-technologies-inc