Clustered regularly interspaced short palindromic repeats (CRISPR) and a CRISPR associated protein (Cas9) comprise a system adapted from bacterial DNA known as CRISPR/Cas9. The CRISPR/Cas9 system act as an adaptive immune system allowing bacteria to recognize foreign DNA and cut it, destroying an invading virus or pathogen. CRISPR/Cas9 has been adapted to other organisms to make specific cuts in their genomic DNA.
CRISPR/Cas9 technology holds the potential to “edit” a patient’s genome, restoring genes with disease-causing mutations to their normal healthy sequence, deleting disease-causing genes, or improving genes for therapeutic effect across a range of single- and multi-gene disorders. Intellia is developing both ex vivo and in vivo applications of this gene editing technology.
Decades of innovation in cell and gene therapy, RNA modification and stabilization, and oligonucleotide delivery provide a strong foundation to accelerate the clinical translation of CRISPR/Cas9 technology. These innovations, coupled with the continued optimization of the CRISPR/Cas9 system, open the potential to expand CRISPR/Cas9 application across a broad range of diseases.
Ex Vivo Gene Editing
Ex vivo approaches remove cells from a patient (for example, from blood or bone marrow), then modify disease-relevant genes, utilizing the CRISPR/Cas9 system, in those cells. Following which, treated cells are returned to the patient for therapeutic effect.
Near-term ex vivo applications include blood disorders, therapeutic protein production and cancer, focused on such approaches as CAR-T and checkpoint inhibitor regulation. A variety of other applications are also under consideration.
In Vivo Delivery
Longer-term, Intellia is advancing toward delivering gene editing treatments directly to the site of disease. CRISPR/Cas9 in vivo therapeutics could be administered either systemically or locally to reach and correct genes within specific cells of the body. Potential in vivo applications include targeting genes in cells of the eye, central nervous system, muscle, lung and liver. In vivo gene editing could also be used to fight infections or tumors.
Technologies for the potential in vivo delivery of CRISPR/Cas9 include modified lipid nanoparticles, viral vectors and modified RNA, many of which have already been successfully used in the clinic for delivery of nucleic acids. While no one delivery technology will be applicable for all indications, this portfolio of technologies provide the basis for identifying the most appropriate delivery approach for the target indication.