Anti-CRISPR proteins to control editing in human embryos

This technology utilizes anti-CRISPR proteins for efficient spatial and temporal control of gene editing.

Unmet Need: Temporal control of CRISPR/Cas9 for reducing off-target effects

CRISPR-Cas9 is a powerful gene-editing tool that can accurately target and modify specific DNA sequences, potentially correcting disease-causing mutations. However, off-target effects can occur when Cas9 mistakenly cuts DNA at unintended locations, leading to potential harm or unintended consequences. Research indicates that Cas9 activity beyond the first cell cycle leads to mosaicism, wherein cells within an individual have genetic variation. As such, temporal control strategies are needed to minimize the duration of Cas9 activity and, in turn, improve the safety and efficacy of CRISPR-Cas9 gene editing.

The Technology: Anti-CRISPR proteins for temporally regulating Cas9 activity

This technology proposes the use of anti-CRISPR proteins to restrict Cas9 activity to the first cell cycle, for improved spatial and temporal control of gene editing. By blocking or slowing down the activity of Cas9, anti-CRISPR proteins control gene editing and regulate CRISPR activity to increase gene-editing efficiency and reduce off-target gene editing in an embryo. This technology improves the success of gene editing in the human embryo for CRISPR-based gene therapies.

Applications:

• Increased accuracy in gene-editing
• Gene-editing in the human embryo
• Research tool for monitoring CRISPR/Cas9 activity
• Method of regulating CRISPR/Cas9 activity in patients undergoing gene-editing therapies

Advantages:

• Minimizes off-target editing during gene editing of embryos
• Prevents mosaicism during gene editing of embryos
• Increase efficiency of gene editing
• Specific against Cas9 activity
• Spatially and temporally specific, allowing for high-fidelity modulation of CRISPR/Cas9 activity

Lead Inventor:

Dieter M. Egli, Ph.D.

Patent Information:

Patent Pending(US20230295667)

Related Publications:

• Zuccaro, M., Xu, J., Mitchell, C., Marin, D., Zimmerman R., Rana, B., Weinstein, E., King, R.T., Palmerola, K., Smith, M., Tsang, S., Goland R., Jasin, M., Lobo,R., Treff, N., Egli, D. “Allele-specific chromosome removal after Cas9 cleavage in human embryos." Cell, 2020; 183(6): 1650-64.e15

Tech Ventures Reference:

• IR CU21215

• Licensing Contact: Kristin Neuman