Shengdar Q. Tsai

This paper develops a non-viral genome-editing method called STEP-RNPs that effectively treats Angelman syndrome in mice and human neurons, showing functional genetic rescue without off-target effects.

This paper develops a customized CRISPR-Cas9 base editor to correct the ACTA2 R179H mutation in a mouse model of MSMDS, improving survival and rescuing vascular and neurological phenotypes.

The paper uses population-scale GUIDE-seq-2 and CHANCE-seq to analyze how genetic variants affect Cas9 activity, finding frequent context-dependent effects on off-target sites.

This study uses CRISPR to disrupt an inhibitory receptor in NK cells and insert a GD2-targeting CAR, creating potent NK cells against GD2+ melanoma.

This study develops a genome-edited autologous CD34+ cell therapy to induce fetal hemoglobin for sickle cell disease, showing efficient editing, therapeutic HbF levels, and no off-target effects.

The paper introduces CHANGE-seq-BE, a method for sensitive and unbiased profiling of base editor off-target effects in vitro.

This paper describes the optimization of base editing to correct the SMN2 exon 7 mutation in SMA, achieving high editing efficiency and increased SMN protein levels in vitro and in vivo.

The paper develops CRISPRme, a tool that integrates genetic diversity data to assess off-target risks of gene editing, finding allele-specific off-target effects in clinical gRNAs.

This paper compares CRISPR-mediated HDR and PE2 systems in mice to show PE2's higher fidelity in editing a TFBS, leading to more effective tissue-specific gene inactivation.

The paper validates off-target effects of CRISPR/Cas9 in rhesus macaques using error-corrected sequencing, showing that in vitro and in silico methods have limited predictive accuracy.

This study shows that zebrafish dscaml1 is crucial for retinal patterning and oculomotor circuit function, with mutations causing deficits in gaze stabilization and saccade fatigue similar to human ocular motor apraxia.

The paper introduces VIVO, a method to detect off-target mutations from in vivo CRISPR-Cas editing, showing that well-designed gRNAs can edit efficiently without detectable off-targets.