In vivo multiomic Perturb-seq with enhanced nuclear gRNA capture

Zheng, X.; Li, J.; Kim, K.; Simmons, S. K.; Zhao, Z.; Tastemel, M.; Huynh, N.; Qiu, H.; Ye, J.; Whte, C. M.; Levin, J. Z.; Jin, X.

doi:10.64898/2026.03.15.711739

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bioRxiv · 10.64898/2026.03.15.711739

In vivo multiomic Perturb-seq with enhanced nuclear gRNA capture

Zheng, X.·Li, J.·Kim, K.·Simmons, S. K.·Zhao, Z.·Tastemel, M.·Huynh, N.·Qiu, H.·Ye, J.·Whte, C. M.·Levin, J. Z.·Jin, X.

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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.

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Zheng, X., Li, J., Kim, K., Simmons, S. K., Zhao, Z., Tastemel, M., Huynh, N., Qiu, H., Ye, J., Whte, C. M., Levin, J. Z., Jin, X.. 2026-03-17. In vivo multiomic Perturb-seq with enhanced nuclear gRNA capture. https://doi.org/10.64898/2026.03.15.711739

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