By explaining how a single amino acid change produces a hypomorphic PIEZO2 allele, the findings broaden the clinical spectrum of PIEZO2 disorders and offer structural insight into mechanotransduction.
Abstract
PIEZO2 is the principal mechanosensory channel for proprioception, touch, and many interoceptive processes, yet key details of how PIEZO channels convert force into electrochemical signals remain unclear. Here, we report fraternal twins with proprioceptive ataxia and scoliosis who carry an unreported PIEZO2 missense variant (N2434K) in compound heterozygosity with a null variant. Gene-edited mice confirm that N2434K is disease-causing, with in vivo recordings demonstrating deficits in sensory neuron mechanical responses. Despite normal membrane expression, the variant has severely reduced mechanically evoked current, which is suggestive of defective gating. N2434 is conserved between PIEZO1 and PIEZO2 and resides in the cap-pore linker, which bridges the extracellular cap and ion-conducting pore. Computational modeling, site-directed mutagenesis, and single-molecule imaging reveal that this region is essential for channel-wide conformational changes during gating. By explaining how a single amino acid change produces a hypomorphic PIEZO2 allele, our findings broaden the clinical spectrum of PIEZO2 disorders and offer structural insight into mechanotransduction.
It is concluded that bridging the gap between foundational CRISPR research and its real-world applications is imperative and future efforts should focus on democratizing tools via open-source platforms, advancing delivery systems, and fostering sustainable innovation through synthetic biology integration to fully realize the transformative potential of genome editing in organisms beyond model organisms.
S. Sarsaiya, Archana Jain, Jishuang Chen et al.· Biotechnology Advances· 2 citations
It is argued that formation of a tumour-intrinsic niche is a prerequisite for BRAF-mutant CRC seeding to distant organs and that interference with niche formation may help avoid metastatic relapse.
J. Bugter, L. El Bouazzaoui, E. Küçükköse et al.· bioRxiv· 2 citations
This review summarizes emerging therapeutic strategies for EOC, their mechanisms of action, and their potential to overcome treatment resistance, and covers molecularly targeted therapies, immunotherapies, metabolic and epigenetic approaches, cellular and gene therapies, targeted drug-delivery systems, and locoregional and physical modalities.
Zofia Pietrasik, Mikołaj Kapała, Joanna Pietrasik et al.· Cancers· 0 citations
Genetic engineering (GE) and gene editing may endow traits to trees such as increased biomass and the production of novel biomaterials. Long-lived organisms such as trees might be subject to biotechnology-related risks that could be different than those of annual row crops. Those risks could be relevant to production in engineered plantations and beyond plantations to natural forests. Therefore, appropriate risk regulation is important to assure biosafety of commercialized engineered trees. In addition to gene flow via sexual reproduction, vegetative reproduction might play an additional role in environmental "exposure" risk relative to transgene dispersal in GE tree plantations. While vegetative reproduction is beneficial for preserving desired genetic traits during tree propagation, it may lead to proximal clonal spread in the field. Although the environmental risks associated with vegetative reproduction of GE trees are recognized in commercial forestry, there are few field-based environmental risk assessment (ERA) studies on dispersal risks of self-propagated GE trees. GE or gene editing of target genes involved in the vegetative propagation processes may be useful to mitigate environmental risks of clonal spread through vegetative reproduction. This review provides updates for recent field test results of GE and gene edited trees. Gene candidates related to vegetative reproduction including adventitious shooting (AS) and adventitious rooting (AR) are discussed herein as a means to mitigate unintended clonal spread from GE tree plantations.
Findings establish Cas7-11 as a precise and efficient RNA knockdown tool for functional studies in embryonic development and stem cell biology, providing a versatile alternative to DNA-based gene-editing approaches.
Huan Yan, Imtiaz Ul Hassan, Kai Yan et al.· Cell & Bioscience· 0 citations
A new method for surgically removing training examples from a model reveals that as datasets grow, the link between what a model learns and what it produces dissolves.
MIT News · Artificial Intelligence· news.mit.eduAug 17, 2026
