Antisense Oligonucleotide–Mediated MSH3 Suppression Reduces Somatic CAG Repeat Expansion in Huntington’s Disease iPSC–Derived Striatal Neurons

Therapeutic Potential of ASO-Mediated MSH3 Suppression in Huntington’s Disease Academic Background Huntington’s disease (HD) is a neurodegenerative disorder caused by abnormal expansion of the CAG repeat sequence in the huntingtin gene (HTT). This expanded CAG repeat continues to expand somatically over time, driving the onset and progression of th...

Prior Vaccination Prevents Overactivation of Innate Immune Responses During COVID-19 Breakthrough Infection

How COVID-19 Vaccines Affect Immune Responses During Breakthrough Infections Background Introduction As the COVID-19 pandemic continues, an increasing number of infections are “breakthrough infections,” occurring in individuals who have been vaccinated or previously infected with SARS-CoV-2. Although vaccination has significantly reduced the risk o...

Ciliopathies: Undocking of an Extensive Ciliary Network Induces Proteostasis and Cell Fate Switching Resulting in Severe Primary Ciliary Dyskinesia

Research on Ciliary Diseases: The Role of CCDC39/CCDC40 Heterodimer in Primary Ciliary Dyskinesia Academic Background Primary Ciliary Dyskinesia (PCD) is a rare monogenic disorder characterized by chronic respiratory infections, infertility, and organ laterality defects. Although more than 50 genes associated with PCD have been identified, mutation...

Selective Abrogation of S6K2 Identifies Lipid Homeostasis as a Survival Vulnerability in MAPK Inhibitor–Resistant NRAS-Mutant Melanoma

Academic Background NRAS-mutant (NRASmut) melanoma is a highly aggressive tumor type, accounting for nearly 30% of all melanoma cases. NRAS is an oncogene that persistently activates the mitogen-activated protein kinase (MAPK) signaling pathway, which plays a critical role in melanoma development. However, despite extensive research on MAPK pathway...

Age-Dependent Macropinocytosis Drives Resistance to KRAS-G12D–Targeted Therapy in Advanced Pancreatic Cancer

Academic Background and Problem Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive cancer with an extremely low five-year survival rate, primarily due to late diagnosis and limited treatment options. Approximately 95% of PDAC patients harbor KRAS mutations, with the KRAS-G12D mutation being the most common. Although KRAS mutations have long b...

High-Throughput Discovery of Inhibitory Protein Fragments with AlphaFold

High-Precision Prediction of Protein Fragment Inhibitory Activity: The Application of FragFold Academic Background Protein interactions play a crucial role in cellular life activities, and peptides or protein fragments can regulate protein functions by binding to specific protein interfaces, even acting as inhibitors. Recent developments in high-th...