CRISPR is a powerful genome-engineering tool with two main components: the Cas endonuclease (enzyme that cuts DNA) protein, and the guide RNA that tells the protein where in the DNA to cut. By changing the nucleic acid sequence of the guide RNA, the Cas protein can be targeted to any gene, allowing for specific DNA manipulation. This powerful tool opens the possibility of changing the DNA of affected patients, opening the door for permanent cures of genetic diseases.
Must arrive simultaneously or become ineffective
Susceptible to degradation>
Higher dosing levels may be required
10 to 15 years in system
Unwanted Iimmune response
Failure of individually expressed components to bind and form active CRISPR complex.
Persistent expression of components such as Cas9 enzymes in cells.
The Incisive Delivery System™ (IDS) offers significant advantages over other modes of CRISPR delivery, namely, nucleic acid or viral delivery techniques.
The IDS delivers the CRISPR ribonucleoprotein (RNP) complex: the pre-assembled protein and guide RNA components, allowing quick on-target action of the cargo, followed by natural degradation and clearance of these components by existing cell mechanisms. Since the protein and guide RNA are already pre-complexed into the ribonucleoprotein (RNP), the two pieces do not need to find each other inside the cell, allowing for increased efficiency and efficacy, before being degraded and cleared after making the edit to the DNA.
This degradation is an important step in gene editing, as the RNP complex may be capable of off-target cutting of the DNA if it remains active for a long period of time. Delivery of the active RNP allows for quick action (cutting) and quick clearance of the components, decreasing the risk of off-target effects.
The IDS platform is compatible with any combination of endonucleases and guide RNAs. By changing the guide RNA sequence, it can be used to deliver cargo that targets almost anywhere in the human genome.
Delivers functional CRISPR components
Enables delivery of multiple genetic cargoes
Alleviates in cell production and failed connections
Unlike AAV, the body does not produce antibodies to LNPs
The Incisive Delivery System™ is compatible with any combination of endonucleases and guide RNAs. By changing the guide RNA sequence, it can be used to deliver cargo that targets almost anywhere in the human genome.