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Author

John G Doench

Broad Institute

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Open access Aug 2026

Dynamic inositol pyrophosphate synthesis is a targetable therapeutic opportunity in ovarian cancer

We previously reported that the phosphate exporter XPR1 is required to prevent toxic phosphate accumulation in ovarian cancer cells. To guide therapeutic development, we sought to systematically compare potential strategies to inhibit XPR1: directly targeting the phosphate efflux channel, targeting its partner protein...

Daniel P. Bondeson, David Husselbee, Saoirse Hanbury et al. · 0 citations
Open access Aug 2026

Methylation Mesa define functional regulatory elements for targeted gene activation

DNA methylation regulates transcription, yet the demethylation of canonical elements like promoter CpG islands exhibits inconsistent correlations with gene activation. We hypothesize that causal regulatory elements are defined by biophysical hypersensitivity. Profiling 24 whole-genome bisulfite sequencing samples acros...

Y.-V. Liu, J. Suryatenggara, H. Wong et al. · 0 citations
#gene editing Open access Sep 2026

Combinatorial CRISPR/Cas12a excises targeted loci in the mammalian genome at very low efficiency

Findings indicate that the Cas12a system does not yield locus excision at the efficiency required for sensitive negative selection assays, and showed no meaningful correlation between gRNA efficiency, orientation, GC content, or cut site geometry and the success of locus excision.

N. Anvar, Zsofia M. Szegletes, R. Steger et al. · 0 citations
Jul 2026

Abstract PR006: Target discovery in rare cancers enabled by transcriptome-based virtual CRISPR screening

It is demonstrated that machine learning applied to transcriptomic data can uncover novel cancer vulnerabilities and actionable targets in individual tumors, even in the absence of functional screening, which may represent a scalable approach to advance precision oncology in rare and/or under-characterized cancer types...

Ananthan Sadagopan, Bingchen Li, Jiao Li et al. · 0 citations
Jul 2026

Abstract PR012: GLIO-1 is a selective DHODH inhibitor that is effective in IDH-mutant gliomas and KDM6-mutated cancers

An selective, on-target, and well-tolerated DHODH inhibitor, GLIO-1, that is effective in IDH-mutant gliomas is developed and nominated as a new pan-cancer biomarker and targeted therapy pairing, KDM6A inactivation and GLIO-1, that is poised for clinical translation.

Alexander C-Y. Tsai, Mathew D. Lin, V. Puliyappadamba et al. · 0 citations
Jul 2026

Abstract B083: GLIO-1 is a selective DHODH inhibitor that is effective in IDH-mutant gliomas and KDM6-mutated cancers

An selective, on-target, and well-tolerated DHODH inhibitor, GLIO-1, that is effective in IDH-mutant gliomas is developed and nominated as a new pan-cancer biomarker and targeted therapy pairing, KDM6A inactivation and GLIO-1, that is poised for clinical translation.

Alexander C-Y. Tsai, Mathew D. Lin, V. Puliyappadamba et al. · 0 citations
Open access Jul 2026

Direct comparison of CRISPR knockout and interference with Perturb-seq

CRISPR knockout (CRISPRko) and CRISPR interference (CRISPRi) are two workhorse technologies for loss-of-function studies, yet direct comparisons between the two are scant relative to their widespread adoption. Here, we establish benchmarking libraries for Cas9-based CRISPRko and CRISPRi screens using Perturb-seq as the...

Laura M Drepanos, Berta Escude Velasco, Abigail J Chase et al. · 1 citation
Open access Aug 2026

Optimized parameters for CRISPR-Cas9 interference library design.

This work compares the performance of multiple KRAB domain systems, develops an updated CRISPRi-specific on-target scoring scheme, and quantitatively characterize off-target effects associated with seed-sequence patterns.

Smriti Srikanth, Fengyi Zheng, Laura M Drepanos et al. · 0 citations

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