In vivo multiomic Perturb-seq with enhanced nuclear gRNA capture

Xinhe Zheng; Jiwen Li; Kwanho Kim; Sean K Simmons; Ziyan Zhao; Melodi Tastemel; Nhan Huynh; Huixian Qiu; Juntong Ye; Cassandra M White; Joshua Z Levin; Xin Jin

doi:10.64898/2026.03.15.711739

In vivo multiomic Perturb-seq with enhanced nuclear gRNA capture

bioRxiv [Preprint]. 2026 Mar 17:2026.03.15.711739. doi: 10.64898/2026.03.15.711739.

Authors

Xinhe Zheng^{1

2}, Jiwen Li^{1

2}, Kwanho Kim³, Sean K Simmons³, Ziyan Zhao^{1

2}, Melodi Tastemel^{1

2}, Nhan Huynh^{1

2}, Huixian Qiu^{1

2}, Juntong Ye^{1

2}, Cassandra M White^{1

2}, Joshua Z Levin³, Xin Jin^{1

2}

Affiliations

¹ Howard Hughes Medical Institute, Chevy Chase, MD, USA.
² Department of Neuroscience, Dorris Neuroscience Center, Scripps Research, La Jolla, CA, USA.
³ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

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.

Publication types

Preprint

Abstract

Publication types

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