Base editor screens for in situ mutational scanning at scale

NZ Lue, BB Liau - Molecular cell, 2023 - cell.com
A fundamental challenge in biology is understanding the molecular details of protein
function. How mutations alter protein activity, regulation, and response to drugs is of critical …

Phage-assisted evolution of highly active cytosine base editors with enhanced selectivity and minimal sequence context preference

E Zhang, ME Neugebauer, NA Krasnow… - Nature …, 2024 - nature.com
TadA-derived cytosine base editors (TadCBEs) enable programmable C• G-to-T• A editing
while retaining the small size, high on-target activity, and low off-target activity of TadA …

Brainwide silencing of prion protein by AAV-mediated delivery of an engineered compact epigenetic editor

EN Neumann, TM Bertozzi, E Wu, F Serack, JW Harvey… - Science, 2024 - science.org
Prion disease is caused by misfolding of the prion protein (PrP) into pathogenic self-
propagating conformations, leading to rapid-onset dementia and death. However …

Post-translational modification-centric base editor screens to assess phosphorylation site functionality in high throughput

PH Kennedy, A Alborzian Deh Sheikh, M Balakar… - Nature …, 2024 - nature.com
Signaling pathways that drive gene expression are typically depicted as having a dozen or
so landmark phosphorylation and transcriptional events. In reality, thousands of dynamic …

[HTML][HTML] Base editing screens define the genetic landscape of cancer drug resistance mechanisms

MA Coelho, ME Strauss, A Watterson, S Cooper… - Nature Genetics, 2024 - nature.com
Drug resistance is a principal limitation to the long-term efficacy of cancer therapies. Cancer
genome sequencing can retrospectively delineate the genetic basis of drug resistance, but …

Assigning functionality to cysteines by base editing of cancer dependency genes

H Li, T Ma, JR Remsberg, SJ Won… - Nature chemical …, 2023 - nature.com
Covalent chemistry represents an attractive strategy for expanding the ligandability of the
proteome, and chemical proteomics has revealed numerous electrophile-reactive cysteines …

Multimodal scanning of genetic variants with base and prime editing

O Belli, K Karava, R Farouni, RJ Platt - Nature Biotechnology, 2024 - nature.com
Mutational scanning connects genetic variants to phenotype, enabling the interrogation of
protein functions, interactions and variant pathogenicity. However, current methodologies …

Unbiased interrogation of functional lysine residues in human proteome

Y Bao, Q Pan, P Xu, Z Liu, Z Zhang, Y Liu, Y Xu, Y Yu… - Molecular Cell, 2023 - cell.com
CRISPR screens have empowered the high-throughput dissection of gene functions;
however, more explicit genetic elements, such as codons of amino acids, require thorough …

Analyzing the functional effects of DNA variants with gene editing

S Cooper, S Obolenski, AJ Waters, AR Bassett… - Cell Reports …, 2024 - cell.com
Continual advancements in genomics have led to an ever-widening disparity between the
rate of discovery of genetic variants and our current understanding of their functions and …

Joint genotypic and phenotypic outcome modeling improves base editing variant effect quantification

J Ryu, S Barkal, T Yu, M Jankowiak, Y Zhou… - Nature …, 2024 - nature.com
CRISPR base editing screens enable analysis of disease-associated variants at scale;
however, variable efficiency and precision confounds the assessment of variant-induced …