98%
921
2 minutes
20
Loss-of-function genetic tools are widely applied for validating therapeutic targets, but their utility remains limited by incomplete on- and uncontrolled off-target effects. We describe artificial RNA interference (ARTi) based on synthetic, ultra-potent, off-target-free shRNAs that enable efficient and inducible suppression of any gene upon introduction of a synthetic target sequence into non-coding transcript regions. ARTi establishes a scalable loss-of-function tool with full control over on- and off-target effects.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10409502 | PMC |
http://dx.doi.org/10.7554/eLife.84792 | DOI Listing |
J Control Release
September 2025
Laboratory of Precision and Nanomedicine, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 14b, 50411 Tartu, Estonia; Materials Research Laboratory, University of California, Santa Barbara, CA 93106, USA. Electronic address:
Most chemotherapeutics distribute non-specifically throughout the body, resulting in off-target toxicities. Nanoparticle (NP) formulations provide a strategy to improve drug delivery by extending circulation time, protecting therapeutic agents from degradation, and enabling controlled release. However, delivering NPs effectively to solid tumors remains challenging due to the barriers within the tumor microenvironment.
View Article and Find Full Text PDFStem Cell Res
September 2025
Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address:
Cardiomyopathies, a leading cause of mortality, are associated with dysfunctional intercalated discs, which connect neighbouring cardiomyocytes and ensure proper contractility. In human cardiac diseases, loss-of-function mutations of the intercalated disc-associated protein Nebulin-Related Anchoring Protein (NRAP) have been reported. NRAP plays a crucial role in myofibril assembly and mechanotransduction, however, its regulatory functions remain unclear.
View Article and Find Full Text PDFAdv Sci (Weinh)
September 2025
Department of Chemical and Biological Engineering, Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science & Technology, Hong Kong, 999077,
Breast cancer (BC), characterized by its heterogeneity and diverse subtypes, necessitates personalized treatment strategies. This study presents MF3Ec-TBPP nanoparticles (NPs) as a promising approach, integrating an aggregation-induced emission (AIE)-based photosensitizer, TBPP, with the MF3Ec aptamer to enhance targeted photodynamic therapy (PDT) for Luminal A subtype BC cells. The nanoparticles also feature a 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) shell and dipalmitoyl phosphatidylcholine (DPPC), which stabilize the structure and inhibit singlet oxygen generation, effectively reducing off-target effects and protecting healthy tissues.
View Article and Find Full Text PDFPlant Cell Environ
September 2025
State Key Laboratory of Tree Genetics and Breeding, Co-Innovation Center for Sustainable Forestry in Southern China, Bamboo Research Institute, Key Laboratory of National Forestry and Grassland Administration on Subtropical Forest Biodiversity Conservation, School of Life Sciences, Nanjing Forestry
CRISPR ribonucleoprotein (RNP)-mediated genome editing offers a transgene-free platform for precise genetic modification in diverse herbaceous and tree species, including rice, wheat, apple, poplar, oil palm, rubber tree and grapevine. However, its application in woody plants faces distinct challenges, notably inefficient delivery and regeneration difficulties, particularly in species such as bamboo. While some of these issues also occur in herbaceous plants, they are often significantly more complex in woody species due to factors such as intricate cell wall architecture, widespread recalcitrant genotypes and inherent limitations of current delivery platforms.
View Article and Find Full Text PDFLab Chip
September 2025
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02215, USA.
CRISPR technology offers an entirely new approach to therapeutic development because it can target specific nucleotide sequences with high specificity, however, preclinical animal models are not useful for evaluation of their efficacy and potential off-target effects because of high gene sequence variations between animals and humans. Here, we explored the potential of using the CRISPR effector Cas13 to develop a new therapeutic approach for influenza A virus (IAV) infections based on its ability to specifically and robustly cleave single-strand viral RNA using a complementary CRISPR RNA (crRNA). We engineered crRNAs to target highly conserved regions in the IAV genome to create a potential pan-viral treatment strategy.
View Article and Find Full Text PDF