Mike A. Firth

CRISPR-Mediated Linearization of IDLV Donor Enables Precise Targeted Integration in Human Hematopoietic Stem Cells

This paper introduces TILV, a CRISPR-assisted method for precise targeted integration of transgenes in human hematopoietic stem cells using IDLV donors, showing improved efficiency and minimal impact on cell viability.

Single-Cell and Tissue-Specific CRISPR Editing Analyses Unveil New Insights to Off-Targets and Translocations

The paper analyzes CRISPR-Cas9 off-target mutations and translocations at single-cell and tissue-specific levels in mice, revealing context-dependent variability in editing outcomes.

Enhanced γ-globin reactivation and sickle cell correction through a repressor-to- activator motif switch in the HBG1/2 promoters

This paper demonstrates that replacing the BCL11A repressor binding site with a TAL1:GATA1 activator motif in HBG1/2 promoters enhances γ-globin reactivation and corrects sickle cell disease in hematopoietic stem/progenitor cells.

An aptamer-mediated base editing platform for simultaneous knock-in and multiple gene knockout for allogeneic CAR-T cells generation

This paper introduces a base editing platform for simultaneous gene knockout and transgene integration in T cells, showing higher efficiency and reduced chromosomal translocations compared to CRISPR-Cas9.

Epigenetic modulators link mitochondrial redox homeostasis to cardiac function

The paper shows that IDH2, a mitochondrial enzyme, acts as a major antioxidant defense in cardiomyocytes, with its activity compensating for reduced expression in heart failure, and identifies an epigenetic mechanism linking oxidative stress to cardiac function.

Simultaneous inhibition of DNA-PK and Pol{Theta} improves integration efficiency and precision of genome editing

This study identifies AZD7648 and Pol{Theta} inhibitors as a combination (2iHDR) that enhances CRISPR-Cas9 integration efficiency and precision by targeting DNA-PK and MMEJ repair pathways.

Harnessing DSB repair to promote efficient homology-dependent and -independent prime editing

This paper develops two prime editing strategies using DSB repair to improve genomic insertion efficiency and purity, expanding the prime editing toolkit.

In vivo CRISPR-Cas gene editing with no detectable genome-wide off-target mutations

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.