We apply synthetic biology principles for safe and effective cardiac remuscolarization via cell therapy
Ongoing Projects
We are optimizing forward programming methods based on inducible transgene overexpression
We are developing methods based on inducible CRISPR/Cas9 and engineered sgRNA scaffolds to perform orthogonal screens of cell reprogramming factors
We are optimizing forward programming methods based on inducible transgene overexpression
We are developing methods based on inducible CRISPR/Cas9 and engineered sgRNA scaffolds to perform orthogonal screens of cell reprogramming factors
Earlier Contributions
We applied gene editing approaches to improve the safety and efficacy of cardiac regeneration therapies based on hPSC-CMs, specifically to reduce the arrhythmogenicity of hPSC-CMs. Through RNA-seq analysis of hPSC-CM maturation in vivo, we selected several candidate genes for genome editing experiments. After examining more than a dozen hPSC lines, we identified a combination of three knockouts (HCN4, CACNA1H, and NCX) and one overexpression (KCNJ2) that resulted in quiescent yet excitable hPSC-CMs, MEDUSA, which showed no engraftment arrhythmia. In parallel, we contributed to a project that improved hPSC-CM engraftment and maturation through co-transplantation with epicardial supporting cells, as well as a project that identified a drug combination (Amiodarone and Ivabradine) capable of mitigating engraftment arrhythmia.
We co-developed an optimized inducible overexpression (opti-ox) platform based on dual gene targeting into safe genomic harbor of a doxycycline-inducible cDNA platform. The potential of this technology was then exemplified by forcing expression of developmental transcription factors in hPSCs, which allowed the efficient derivation of several mature cell types including skeletal muscle, neurons, and oligodendrocytes. Our patent based on opti-ox technologies has been licensed to bit.bio ltd, a cell engineering and manufacturing company based in Cambridge, UK.
We applied gene editing approaches to improve the safety and efficacy of cardiac regeneration therapies based on hPSC-CMs, specifically to reduce the arrhythmogenicity of hPSC-CMs. Through RNA-seq analysis of hPSC-CM maturation in vivo, we selected several candidate genes for genome editing experiments. After examining more than a dozen hPSC lines, we identified a combination of three knockouts (HCN4, CACNA1H, and NCX) and one overexpression (KCNJ2) that resulted in quiescent yet excitable hPSC-CMs, MEDUSA, which showed no engraftment arrhythmia. In parallel, we contributed to a project that improved hPSC-CM engraftment and maturation through co-transplantation with epicardial supporting cells, as well as a project that identified a drug combination (Amiodarone and Ivabradine) capable of mitigating engraftment arrhythmia.
We co-developed an optimized inducible overexpression (opti-ox) platform based on dual gene targeting into safe genomic harbor of a doxycycline-inducible cDNA platform. The potential of this technology was then exemplified by forcing expression of developmental transcription factors in hPSCs, which allowed the efficient derivation of several mature cell types including skeletal muscle, neurons, and oligodendrocytes. Our patent based on opti-ox technologies has been licensed to bit.bio ltd, a cell engineering and manufacturing company based in Cambridge, UK.