At Intellia we are building a fully integrated, product-driven biotechnology company that is focused on developing and commercializing potentially curative genome editing treatments that can positively transform the lives of people living with severe and life-threatening diseases. Our approach to advancing the broad potential of genome editing includes our plans to:
- Focus on sentinel indications that enable us to fully develop the potential of the CRISPR/Cas9 system
- Aggressively pursue in vivo liver indications to develop therapeutics rapidly with existing delivery technology
- Continue to develop and expand our ex vivo therapeutic programs through our eXtellia division
- Continue to leverage strategic partnerships to accelerate clinical development
- Grow our leadership position in the field of genome editing
A Multi-Faceted, Risk-Diversified Strategy
To maximize our opportunity to rapidly develop clinically successful products, we have applied a risk-mitigated approach to selecting our initial disease targets, or “sentinel indications.” We chose those indications that have significant unmet medical needs, using four primary selection criteria:
- The type of edit involved
- How it will be delivered – in vivo or ex vivo
- The presence of established therapeutic endpoints
- The potential benefits compared to existing therapies
These selection criteria position us to build a pipeline where we are not reliant on any single delivery technology or editing approach for success. In addition, we believe we can apply the learnings from these sentinel indications to inform our selection of subsequent indications and targets of interest. We believe this approach serves to increase our probabilities of success and broadens the opportunity for potential strategic alliances to accelerate clinical development.
The CRISPR/Cas9 system allows us to make three general types of edits: knockout, repair and insertion. Different diseases can be addressed using one or more of these editing strategies, depending on the particular genetic defect and the spectrum of genetic defects within a patient population.
- Edits that cause loss of function.
- Can be applied to genes that make harmful proteins or disease causing viruses.
- Edits that repair disease associated gene mutations.
- Can be applied to single point mutations restricted to a small region of DNA.
- Edits that correct disease associated gene.
- Can be applied to insert a functional gene or replace part of a gene where mutations are distributed across a large region of DNA.
The CRISPR/Cas9 system can be applied in two ways: in vivo and ex vivo.
In Vivo Applications
Ex Vivo Applications
The critical element in developing effective CRISPR/Cas9 treatments is in creating or enhancing the delivery methods for the technology. Intellia is initially targeting two distinct delivery methods:
- For in vivo applications, delivering the CRISPR/Cas9 components via Lipid Nanoparticle (LNPs). Certain LNPs have demonstrated efficacy, safety and favorable tolerability and are currently used as a delivery system for therapeutic small interfering RNA, or siRNA, as well as therapeutic messenger RNA, or mRNA. With our team’s expertise with LNP delivery technology, we expect to be able to readily translate the LNPs that we are using for our preclinical development to clinical development in humans.
- For ex vivo applications, delivering the CRISPR/Cas9 components by electroporation, an electrical charge-based technique for delivering molecules into cells.
We are actively investigating additional delivery methods, including evaluating multiple viral delivery vectors, which are viruses engineered to carry non-viral nucleic acids to patients’ cells, as well as several newer technologies for delivery to cells ex vivo, which may provide advantages in delivery efficiency or cell viability.
Intellia’s broad-based licensed patent portfolio encompasses foundational filings on the use of CRISPR/Cas9 systems for genome editing, improvements and modifications of these systems and their components for human therapeutic use; lipid nanoparticle technologies for delivering protein/nucleic acid complexes and RNA into cells; and cell expansion technology relevant to stem cell-based therapies.