In vivo multiomic Perturb-seq with enhanced nuclear gRNA capture

bioRxiv (Cold Spring Harbor Laboratory) 2026 Preprint Open access

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Authors: Xinhe Zheng, Jie Li, Kwanho Kim, Sean K. Simmons, Ziyan Zhao, Melodi Tastemel, Nhan Huynh, Huixian Qiu, Juntong Ye, Cassandra M Whte, Joshua Zev Levin, Xin Jin
DOI: 10.64898/2026.03.15.711739
Cited by: 1
References: 30

Abstract

Abstract In vivo CRISPR screening with joint transcriptomic and chromatin readouts has been limited by inefficient recovery of gRNAs from nuclei. Here, we developed in vivo multiomic Perturb-seq, an effective platform combining nuclear transcript anchoring with gRNA-specific capture and amplification to enable high-fidelity, high-recovery gRNA assignment and scalable perturbation-resolved single-nucleus multiomics. Applying this platform to interrogate neurodevelopmental disorder risk genes in the developing cortex reveals cell-type-specific transcriptomic and epigenomic perturbation phenotypes.

Fields of Study & Subjects

CRISPR and Genetic Engineering Single-cell and spatial transcriptomics Genomic variations and chromosomal abnormalities

Publication details

Journal / source
bioRxiv (Cold Spring Harbor Laboratory)
Publisher
openRxiv
Publication date
17 March 2026
Language
EN
Document type
Preprint