Aug 2026· npj Drug Discovery· Vol 3· 0 citations· 56 references
Medicine
TL;DR
The findings suggest that triple potentiation can significantly enhance functional restoration of poorly responsive gating mutants, thereby uncovering novel avenues for therapeutic development.
Abstract
The Trikafta drug combination, comprising the corrector tezacaftor (VX-661), the potentiator ivacaftor (VX-770) and the dual corrector/potentiator elexacaftor (VX-445), has been FDA-approved for treatment of cystic fibrosis caused by ~300 cystic fibrosis transmembrane conductance regulator (CFTR) mutations. Nevertheless, several CFTR variants exhibit limited response to Trikafta. To address this therapeutic gap, we investigated whether the potentiator activity of VX-445 can complement the VX-770 and preclinical “co-potentiators” activity in partially responsive CFTR mutants. Functional clustering of clinical and preclinical potentiator profiles suggests that VX-445 represents a distinct potentiator class, an inference supported by its additivity with both VX-770/VX-770-like potentiators and co-potentiators across five CFTR mutants in bronchial epithelia. This concept was further validated in gene-edited 16HBE and primary human nasal epithelia, expressing G551D-, N1303K-, and W1282X-CFTR, the 3rd, 4th, and 6th most common CF-mutations, respectively, and was confirmed at the single-channel level. Moreover, we present the development of a novel series of co-potentiator compounds that are derived from our previously described 4172 corrector scaffold, which exhibit low micromolar potency. Our findings suggest that triple potentiation can significantly enhance functional restoration of poorly responsive gating mutants, thereby uncovering novel avenues for therapeutic development.
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
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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.
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Huan Yan, Imtiaz Ul Hassan, Kai Yan et al.· Cell & Bioscience· 0 citations
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MIT News · Artificial Intelligence· news.mit.eduAug 17, 2026