Discovery of diverse CRISPR-Cas systems and expansion of the genome engineering toolbox

EV Koonin, JS Gootenberg, OO Abudayyeh - Biochemistry, 2023 - ACS Publications
CRISPR systems mediate adaptive immunity in bacteria and archaea through diverse
effector mechanisms and have been repurposed for versatile applications in therapeutics …

Sequence modeling and design from molecular to genome scale with Evo

E Nguyen, M Poli, MG Durrant, B Kang, D Katrekar… - Science, 2024 - science.org
The genome is a sequence that encodes the DNA, RNA, and proteins that orchestrate an
organism's function. We present Evo, a long-context genomic foundation model with a …

Prediction of on-target and off-target activity of CRISPR–Cas13d guide RNAs using deep learning

HH Wessels, A Stirn, A Méndez-Mancilla, EJ Kim… - Nature …, 2024 - nature.com
Transcriptome engineering applications in living cells with RNA-targeting CRISPR effectors
depend on accurate prediction of on-target activity and off-target avoidance. Here we design …

A versatile CRISPR-Cas13d platform for multiplexed transcriptomic regulation and metabolic engineering in primary human T cells

V Tieu, E Sotillo, JR Bjelajac, C Chen, M Malipatlolla… - Cell, 2024 - cell.com
CRISPR technologies have begun to revolutionize T cell therapies; however, conventional
CRISPR-Cas9 genome-editing tools are limited in their safety, efficacy, and scope. To …

[HTML][HTML] Approaches to probe and perturb long noncoding RNA functions in diseases

G Wang, Y Lee-Yow, HY Chang - Current Opinion in Genetics & …, 2024 - Elsevier
Long noncoding RNAs (lncRNAs) are a class of RNA molecules exceeding 200 nucleotides
in length that lack long open-reading frames. Transcribed predominantly by RNA …

Efficient combinatorial targeting of RNA transcripts in single cells with Cas13 RNA Perturb-seq

HH Wessels, A Méndez-Mancilla, Y Hao, E Papalexi… - Nature …, 2023 - nature.com
Pooled CRISPR screens coupled with single-cell RNA-sequencing have enabled systematic
interrogation of gene function and regulatory networks. Here, we introduce Cas13 RNA …

CRISPR-dCas13d-based deep screening of proximal and distal splicing-regulatory elements

Y Recinos, D Ustianenko, YT Yeh, X Wang… - Nature …, 2024 - nature.com
Pre-mRNA splicing, a key process in gene expression, can be therapeutically modulated
using various drug modalities, including antisense oligonucleotides (ASOs). However …

Programmed RNA editing with an evolved bacterial adenosine deaminase

H Yan, W Tang - Nature Chemical Biology, 2024 - nature.com
Programmed RNA editing presents an attractive therapeutic strategy for genetic disease. In
this study, we developed bacterial deaminase-enabled recoding of RNA (DECOR), which …

Modeling CRISPR-Cas13d on-target and off-target effects using machine learning approaches

X Cheng, Z Li, R Shan, Z Li, S Wang, W Zhao… - Nature …, 2023 - nature.com
A major challenge in the application of the CRISPR-Cas13d system is to accurately predict
its guide-dependent on-target and off-target effect. Here, we perform CRISPR-Cas13d …

Repurposing CRISPR-Cas13 systems for robust mRNA trans-splicing

DN Fiflis, NA Rey, H Venugopal-Lavanya… - Nature …, 2024 - nature.com
Type VI CRISPR enzymes have been developed as programmable RNA-guided Cas
proteins for eukaryotic RNA editing. Notably, Cas13 has been utilized for site-targeted single …