CRISPR editing of chromosome content in human embryos

This technology is a CRISPR-based approach for specific removal of a chromosome for prevention of trisomies (chromosome gains).

Unmet Need: Method for correcting trisomies in affected embryos

Errors in the production of germ cells can cause mis-segregation of genetic material, known as aneuploidy. Germ cell aneuploidy dramatically increases with advanced maternal age, leading to miscarriages, genetic defects, and reduced fertility. Current technology enables aneuploid embryos to be identified and eliminated in in vitro fertilization clinics. However, there is currently no corrective therapy for these embryos, making aneuploidy an insurmountable reproductive obstacle for some patients. Recently, CRISPR/Cas9 gene editing has emerged as a promising method to modify chromosome content at the time of conception without discarding embryos. This molecular tool has yet to be harnessed for the specific removal of a chromosome for disease-correcting applications.

The Technology: CRISPR-based chromosome removal in human embryos

This technology is a CRISPR-based strategy for removing a disease-causing supernumerary chromosome at and shortly after fertilization. This method requires one cut by Cas9, which can be directed in an allele-specific manner, to eliminate an entire chromosome arm with a high efficiency of approximately 50% with a single guide. The combination of several guides is expected to increase efficiency of removal.

Applications:

• In vitro fertilization
• Treatment of aneuploidies during in vitro fertilization
• Treatment of aneuploidies in cancer and aging
• Research model for studying elimination of aneuploidies and chromosome stability
• Tool for generating genetically modified plants and animals
• Genetics and developmental biology research tool

Advantages:

• Enables removal of trisomies without discarding embryos
• Enables allele-specific chromosome removal
• Demonstrates high efficiency (~50%) in human embryos
• Corrects aneuploidies in embryos used for in vitro fertilization and improves fertility in those with advanced maternal age
• Can potentially be expanded to eliminate several chromosomes

Lead Inventor:

Dieter (Dietrich) Egli, Ph.D.

Patent Information:

Patent Pending

Related Publications:

• Zuccaro MV, Xu J, Mitchell C, Marin D, Zimmerman R, Rana B, Weinstein E, King RT, Palmerola KL, Smith ME, Tsang SH, Goland R, Jasin M, Lobo R, Treff N, Egli D. “Allele-specific chromosome removal after Cas9 cleavage in human embryos” Cell. 2010 Dec 10; 183(6): 1650-1664.

Tech Ventures Reference:

• IR CU20109, CU20250

• Licensing Contact: Ron Katz