CRISPR-Cas9 genome engineering strategies
Cas9 is a naturally occurring protein found in the immune system of certain bacteria, where it scans the host genome checking for foreign, invading DNA from bacteriophages, which are viruses that attack bacteria, and cleaves or “cuts” the foreign DNA from its location in the genome.
Scientists recognized the potential power of such a function and used it to create a gene editing mechanism for use in plant and animal cells. Using Cas9 as a pair of molecular scissors, it can be directed to any desired location within a genome to cut or modify targeted DNA.
At the Wyss Institute, researchers are working in collaboration with other scientists and institutions to innovate an arsenal of powerful genome engineering tools based upon CRISPR-Cas9. Three novel mechanisms that leverage Cas9 functions have emerged that promise to help advance the fields of genome engineering, tissue engineering, and synthetic biology.
Cas9 has been developed at the Wyss Institute as a potential gene therapy strategy for use in higher organisms, including humans. By optimizing CRISPR-Cas9 to allow for insertion, replacement and regulation of targeted genes, gene expression could be altered to reduce the function of the CCR5 receptor which is a primary pathway used by the HIV virus to cripple the immune system, or to repair gene mutations responsible for sickle cell diseases and hemophilia.
A genome editing strategy borne from CRISPR-Cas9 research could offer a potential strategy for controlling insect-borne diseases and invasive plant and animal species. Called a “gene drive” by its inventors at the Wyss Institute, this Cas9 application could be used in species with rapid life and reproductive cycles to effect a desired change in a population, such as eliminating the gene in mosquitos responsible for transmission of malaria. In this way, the gene drive could be used as an important tool to improve environmental and human health alike.
By modifying Cas9 so that instead of cutting DNA it can bind to and activate targeted genes, Wyss Institute researchers have developed a robust, programmable mechanism that can activate genes on demand. The Cas9 gene activator can precisely turn genes from off to on at any desired location in the genome, activating either a single gene or multiple genes that are responsible for cell development and onset of disease.
Cutting-edge innovative technologies have the capacity to provide translational public health solutions that have far-reaching, worldwide opportunities for use. These technologies could also be misused. To address the potential safety, security, and environmental implications involved in the research of emerging biotechnologies, of which many have not yet been characterized with established safety standards to reference, the Wyss Institute has implemented an integrated, multi-tier research review process to ensure that such research is managed through an extensive oversight process. Click here to access the Institute’s Risk Management Plan that ensures biosafety and biosecurity measures on several levels.