ASSAY FOR SAFETY ASSESSMENT OF THERAPEUTIC GENETIC MANIPULATIONS, GENE THERAPY VECTORS AND COMPOUNDS

摘要

The invention is directed to methods of assessing the safety of therapeutic compounds and therapeutic genetic manipulations, including integrating gene therapy vectors and genome editing. In particular, the invention provides a method, wherein the oncogenic potential of therapeutic compounds and therapeutic genetic manipulations, including integrating gene therapy vectors and genome editing, is determined by determining the percentage of differentiation blocked hematopoietic progenitor cells.

主权项

1. A method for assessing oncogenic potential of a recombinant viral construct that integrates into a patient's genome, said method comprising:
a) culturing hematopoietic progenitor cells under conditions that allow their development into mature hematopoietic cells; b) transducing the hematopoietic progenitor cells with the recombinant viral construct; c) continuing to culture the hematopoietic progenitor cells under conditions that allow their development into mature hematopoietic cells for about 10-40 days, and d) determining the percentage of the hematopoietic progenitor cells blocked at an early differentiation stage relative to the total number of the hematopoietic progenitor cells, wherein the early differentiation stage is selected from the group consisting of DN1, DN2, DN3, and DN4.