Most diseases have a strong genetic basis. Thus, gene therapies that directly modulate gene sequence or expression could treat some of the most elusive and intractable diseases. The potential for gene therapies is tremendous; this is reflected by the rapid growth of gene therapy products beginning to reach the market. However, there is no clinically viable way to deliver gene therapies to target cells outside the liver. This is because delivering a gene therapy inside a target cell requires a nanoparticle to overcome a number of challenges.
The drug must find it way to the target cells typically after administration by injection into the skin, muscle, bloodstream or cerebrospinal fluid, or by the gastrointestinal route passing through both hydrophobic and hydrophilic biological environments
It must be directed toward the target cells without significant interaction with non-target tissues and avoiding attack by the immune system.
The drug must be taken up by the target cells through active or passive endocytosis, be released by the endosome, avoid destructive nucleases, and sometimes reach the cell nucleus.
Finally, the drug gets processed by cellular machinery.
Most companies currently utilize viral vectors to deliver genetic drugs. However, viral production is difficult to produce and purify at large scale, cannot deliver large genes, and can only be administered once in a lifetime.
More recently, lipid nanoparticles (LNPs) have emerged as technologies for drug delivery. LNPs utilize natural or synthetic lipid-like materials to encapsulate genetic therapies, protecting these therapies from degradation prior to delivery to the target cell. LNPs are safe and have been approved by the FDA.
Until now, LNPs have only targeted hepatocytes with clinically-relevant efficacy. Guide, working with the Dahlman Lab, has shown that by modifying the characteristics of nanoparticles, it is possible to achieve delivery to non-liver tissues and cell types at safe, therapeutically relevant doses in vivo. Guide’s unique high throughput screening approach can quickly identify nanoparticles for new tissues, enabling new therapeutic targets with no (or minimal) market competition. Guide is expanding its intellectual property portfolio to include delivery to new tissue types and is seeking commercial or academic partners to develop entirely new genetic therapies.