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USU Biochemists Show CRISPR Can Selectively Destroy Cells, a Cancer-Treatment Goal
Cas12a2 enzyme is programmed to identify specific RNA sequences rather than DNA. Upon successful recognition and binding to its target RNA, the protein undergoes a conformational change that unleashes indiscriminate collateral cleavage of intracellular DNA, effectively shredding the genetic material and inducing rapid cell death. In preclinical in vitro and in vivo models, a single administration of this targeted Cas12a2 system suppressed the proliferation of KRAS-mutated cancer cells by 50% and eliminated human papillomavirus (HPV)-infected cells with an efficacy exceeding 90%. Crucially, the intervention demonstrated high specificity, displaying no significant off-target cytotoxicity or damage to healthy tissue. This RNA-triggered DNA-shredding mechanism provides a highly adaptable and potent platform for oncology and virology, shifting the CRISPR paradigm from localized genetic correction to the targeted apoptosis of diseased cells, with future applications potentially expanding to target HIV and other robust infections.
Kadin Crosby, Ryan Jackson and colleagues report newly discovered details demonstrating how CRISPR Cas12a2 can be repurposed to discriminately kill cancer cells in the petri dish and in mice.
Presidential Unsealing and Reporting System for UAP Encounters (PURSUE)
At the direction of President Donald J. Trump, the Department of War is overseeing a multiagency effort to expeditiously find, review, identify, declassify and publicly release unresolved Unidentified Anomalous Phenomena-related records and historical documents in the federal government’s possession./ meta name=.
In Vivo RNA Delivery to Hematopoietic Stem and Progenitor Cells via Targeted Lipid NanoparticlesClick to copy article linkArticle link copied!
A nicely concise paper on antibody-linked lipid nanoparticles which target hematopoietic stem and progenitor cells in vivo, important yet tricky cell types to transduce for hematological gene therapy.
Ex vivo autologous hematopoietic stem cell (HSC) gene therapy has provided new therapies for the treatment of hematological disorders. However, these therapies have several limitations owing to the manufacturing complexities and toxicity resulting from required conditioning regimens. Here, we developed a c-kit (CD117) antibody-targeted lipid nanoparticle (LNP) that, following a single intravenous injection, can deliver RNA (both siRNA and mRNA) to HSCs in vivo in rodents. This targeted delivery system does not require stem cell harvest, culture, or mobilization of HSCs to facilitate delivery. We also show that delivery of Cre recombinase mRNA at a dose of 1 mg kg–1 can facilitate gene editing to almost all (∼90%) hematopoietic stem and progenitor cells (HSPCs) in vivo, and edited cells retain their stemness and functionality to generate high levels of edited mature immune cells.
Yann Le Cun : « Ce que nous construisons, c’est ni plus ni moins que le cortex préfontal des machines »
ENTRETIEN. Pour le chercheur, Prix Turing 2018, la prochaine révolution robotique – celle de systèmes vraiment autonomes et dotés d’une véritable compréhension du réel – n’est possible que si l’on ancre l’IA dans le monde physique.
