Stanley Qi lab @ Stanford Bioengineering
Genome Engineering and Synthetic Biology Laboratory
We believe new engineering will transform biology and medicine, bringing hope to incurable diseases.
We work on technology development for genome engineering, discovery-focused synthetic biology, and epigenetic gene therapy. We aim to develop new technologies for studying the mammalian genome and treating complex diseases.
For technology development, we are interested in novel technologies that reprogram the mammalian genome and epigenome. We developed the first nuclease-dead dCas9 from the natural CRISPR-Cas9 nuclease. We developed a series of CRISPR tools that greatly enriched the CRISPR toolbox and expanded genome engineering beyond editing. These tools include CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa) for targeted gene activation and repression, LiveFISH for live imaging of DNA and RNA, CRISPR-GO for manipulating the 3D genome organization, and miniature Cas (CasMINI) and hyper-efficient Cas12a (hyperCas12a) for in vivo applications. We harness natural molecules for molecular engineering and evolve novel functions. These tools are broadly used by the community for research and and translational applications.
For discovery-focused synthetic biology, we apply synthetic biology to design and engineer molecules and molecular circuits in mammalian cells. We use synthetic systems to study how cells can be rationally designed as an 'engineering' entity and be harnesses for disease treatment. For example, we engineer T cells to detect new antigens to kill cancer cells or stem cells to integrate environment cues to determine cell fate. By engineering at the scale from molecular to cellular to organismal level, we hope to make synthetic biology a better discovery tool.
For epigenetic gene therapy, we combine epigenome engineering, synthetic biology, and disease models to develop novel therapy to treat cancer, neurodegeneration, and complex genetic diseases. We aim to reveal the importance of noncoding elements including enhancers in the regulation of genome and disease. We harness safe and powerful tools to precisely rewrite the epigenome marks to reverse or cure diseases. We developed PAC-MAN as a treatment to influenza and broad variants of SARS-CoV-2. We aim to greatly expand genome and epigenome engineering towards neurodegenerative diseases and complex diseases.
A list of developments in the lab are:
- Development of the first nuclease-dead Cas9 (dCas9) and CRISPR interference (Qi et al. Cell 2013)
- Development of the first CRISPR activation (CRISPRa) in mammalian cells (Gilbert et al. Cell 2013)
- Development of the first CRISPR live cell imaging (Chen et al. Cell 2013)
- CRISPR genome screening (Gilbert et al. Cell 2014)
- Dual gene activation and repression using CRISPR-RNA aptamers (Zalatan et al. Cell 2015)
- Small molecules for enhancing genome editing (Chen et al. Cell Stem Cell 2015)
- Whole-genome CRISPRi screening in bacteria (Peters et al. Cell 2016)
- Chemically inducible CRISPRi and CRISPRa (Gao et al. Nature Methods 2016)
- GPCR-inducible CRISPR genome engineering (Kipniss et al. Nature Communications 2017)
- Combinatorial CRISPRi screening in mammalian cells (Du et al. Nature Methods 2017)
- 3D genome manipulation in mammalian cells (CRISPR-GO) (Wang et al. Cell 2018)
- Genome-wide CRISPR screening in stem cells and neurons (Liu et al. Cell Stem Cell 2018)
- Live cell imaging of DNA and RNA (LiveFISH) (Wang et al. Science 2019)
- Anti-CRISPR for safeguarding genome editing (Nakamura et al. Nature Communications 2019)
- CRISPR-based antivirals for influenza and SARS-CoV-2 (Abbott et al. Cell 2020)
- Genome engineering circuits for detecting and eliminating cancer (Kempton et al. Molecular Cell 2020)
- CRISPR-mediated phase condensation and heterochromatin control (Gao et al. Molecular Cell 2021)
- Miniature CRISPR (CasMINI) (Xu et al. Molecular Cell 2021)