Genome Editing of Human Cells for Biomedical Applications
Krishanu Saha, University of Wisconsin-Madison
The latest breakthrough in genome editing, the clustered regularly interspaced short palindromic repeats (CRISPR) system, applies an editorial eye to the human genome, searching for typos and other infelicities that mar the basic text. Gene editing shows many signs of being cheaper, faster, more accurate, and more widely applicable than older gene editing techniques because of its ability to cut and alter the DNA at almost any genomic site with ease and precision.
This talk will focus on the application of CRISPR genome editing for targeted therapy within the body, so called somatic gene editing. Current frontiers in this field involve 1) nonviral delivery of the CRISPR components to specific cell types and tissues of the body; 2) reduction of imprecise or undesired “off-target” editing at unintended sequences within the human genome; and 3) increased sequence complexity of gene edits. Frontier work with nonviral delivery exploits novel biomaterials and bioconjugate chemistry, while protein engineering and manipulation of DNA repair pathways have been used to generate CRISPR nucleases with higher fidelity. Bioengineers working with CRISPR are expanding our abilities to manipulate multiple genetic loci at once (i.e., multiplexing) and insert novel genetic circuits and functionality. These emerging CRISPR techniques are being applied outside the body with both autologous and allogenic cell sources from patients, as well as in the body via injectable formulations of CRISPR components. Solutions to the problems of inefficient delivery and imprecise editing are likely to usher in a new generation of advanced therapies in the clinic.