Precision Medicine Using CRISPR

Exciting developments in CRISPR/Cas9 gene therapy! Researchers have developed a biomimetic mineralized CRISPR/Cas9 RNA delivery system that addresses the challenge of efficient multiplex gene editing. This all-in-one system is inspired by natural biomineralization and allows for precise control of the coencapsulation ratio between Cas9 mRNA and multiple sgRNAs. It also provides high RNA loading capacity, improved RNA storage stability, and the nanoparticles' surface can be easily functionalized for targeted delivery in vivo at nonliver sites and rapid lysosome escape. Moreover, the nanoparticle can be easily coated with hyaluronic acid for precise and efficient accumulation at the tumor site. In a proof-of-concept, the system demonstrated significant gene-editing at each target gene and promoted apoptosis of HeLa cells in a mouse model, inhibiting tumor growth without noticeable off-target effects in liver tissue. Moreover, there were no signs of toxicity to the mice based on the hematological parameters and they had normal liver and kidney function indices with low inflammation, what was attributed to N1-methylpseudouridine triphosphate substitution of uridine, which reduces the innate immune stimulatory effects of RNA. While coencapsulation of RNA species in viral vectors is difficult due to limited loading capacity, LNPs-based nonviral delivery technologies have made their way into human clinical trials. Still, their low RNA loading and nonspecific targeting to the liver limit their wider application. For these reasons, a novel and innovative strategy like this could revolutionize RNA-based CRISPR/Cas9 gene editing and has a huge potential for advancing gene therapy and cell engineering. Learn more here: https://lnkd.in/enhjhf2h #GeneTherapy #CRISPR #Cas9 #GeneEditing #BiomedicalEngineering #Nanotechnology #nanomaterials #nanoparticles #nanomedicine

ChatGPT for CRISPR 🧬Artificial Intelligence (AI) derived gene editors seem to be outdoing their counterparts in nature. 🧬Gene editors can now push some buttons on their computers instead of searching for CRISPR tools chaffing microbes from hot springs, peat bogs, poo (yes really!!), and even yogurt. 🧬A generative AI tool, specifically "a protein language model" that is a neural network trained on millions of protein sequences is enabling researchers to design CRISPR gene-editing proteins, and then replicate results as expected in the lab....a seamless travel "in silico to in vitro." 🧬The first successful editing of the human genome by proteins designed entirely with machine learning has been sent out for peer-review (https://lnkd.in/gCkNmwu6) 🧬AI is expected to expand the repertoire of editors overcoming the challenges of naturally occurring gene-editing systems in finding diverse and specific targets to edit. 🧬Chatbots such as ChatGPT handling languages after being trained on existing text are now redesigned as CRISPR-designing AIs after being trained on vast arrays of biological data in the form of protein or genome sequences. 🧬A protein language tool ProGen was redesigned in terms of expanding its molecular linguistics to now be able to design ‘guide RNAs’ and this evolved into "OpenCRISPR-1" that has the ability to tap the neural network to design millions of new CRISPR protein sequences that belong to dozens of different families of proteins found in nature.  🧬OpenCRISPR-1 was just as efficient at cutting targeted DNA sequences as a widely used bacterial CRISPR–Cas9 enzyme and it expands applications towards "precision medicine" as AI-generated CRISPR tools may prove better suited for diverse medical applications. https://lnkd.in/gEyzgYRt

FDA approves two gene-modified autologous cell therapies for sickle cell disease, including first that uses CRISPR – paving the way for expanded use of personalized gene-engineered cell therapies. Bespoke autologous cell therapies have a niche as living therapeutics in clinical use cases where immune function and compatibility are paramount for potency. Enter the FDA approval of bluebird bio’ Lyfgenia as well as Vertex Pharmaceuticals’ Casgevy, both for SCD. Although the FDA approval of a gene engineered autologous cell pharmaceutical was first achieved with Novartis’ Kymirah in 2017, the FDA’ approval of Vertex’ Casgevy speaks to its assent of CRISPR-mediated gene editing as meeting safety equipoise. This also paves the way for FDA-sanctioned commercial manufacturing schemes for use of CRISPR gene-engineering technology – in addition to lentiviral transduction – as commercially viable means of manufacturing bespoke personalized gene-engineered cell therapies for use in other catastrophic illnesses with unmet medical needs. Disruptive gene-engineering technologies coupled with open market competition will be drivers of sustainable and accessible living therapeutics treatments and cures now and in future. Congratulations to the legion early innovative scientific discoverers and the risk-taking moxxi of CGT commercial developers to bring these living  pharmaceutical platforms over the marketing approval goal line.