

Victor Tieu
35 posts

@victortieu
CRISPR for better cell therapies @Stanford PhD 🌲 · @UCBerkeley 🐻 Stanley Qi & Crystal Mackall labs







🚨New lab preprint! 🚨 A deep dive to shed light on a long-standing controversy with RNA-targeting CRISPRs: Do they have high levels of collateral (trans) cleavage of other RNAs in the cell ✂️✂️✂️ — or not? New work from talented PhD student #SydneyHart & others in our lab. 📰








SCI members Stanley Qi, Crystal Mackall & team pioneered MEGA, a #CRISPR RNA-editing tool enhancing #CARTcells precision against tumors. stanford.io/3TdepLd @stanleyqilab @MackallLab

MEGA is a CRISPR-Cas13d system that allows for knockdown of gene expression at the genetic level, offering several unique advantages over CRISPR-Cas9 👉 acir.org/weekly-digests… @StanfordMed






MEGA-CRISPR (multiplexed effector guide arrays) is an alternative to CRISPR editing that edits RNA instead of DNA. It swaps the DNA-cutting enzyme Cas9 for an RNA-cutting alternative called Cas13d. As mRNA doesn’t last very long in a cell, any potential mistakes disappear fast. MEGA-CRISPR can shut down the production of multiple proteins, turning off up to 10 genes at once. To showcase the power of this system, a new paper addressed a really important clinical problem: T cell exhaustion in immunotherapy treatment for cancer patients. What this means is that, when either natural or engineered T cells (such as in CAR-T therapy) are chronically activated too many times by a tumor for example, they lose their effectiveness and ultimately stop reacting. The paper tunes exhaustion markers using an antibiotic switch of varying dose, creating a system that can essentially react dynamically and turn genes on/off as a function of a varying input. This system is an important advance because (1) editing mRNA is more versatile & less consequential than editing DNA (2) it can edit very many genes at a time (up to 10) (3) it can tune these many genes on/off using an external input Exciting times ahead for cell therapies in oncology! nature.com/articles/d4158…