Current lipid nanoparticle (LNP) drug delivery technologies are formulated with ingredients such as cholesterol that are destined to accumulate in the liver, which is why many established genetic medicines (such as gene therapy, mRNA vaccines and gene editing technologies) are excreted before they reach their targets. If you want to treat brain diseases or lung diseases, you don't want the delivered drugs to go to the liver. This requires the development of solutions that can target drugs to the right tissues and cells.
| Cat.No. | Product Name | Price |
|---|---|---|
| PMCRL-0016 | Sox2 circRNA-LNP | Inquiry |
| PMCRL-0017 | Oct4 circRNA-LNP | Inquiry |
| PMCRL-0018 | Klf circRNA-LNP | Inquiry |
| PMCRL-0019 | c-Myc circRNA-LNP | Inquiry |
| PMCRL-0020 | Lin28 circRNA-LNP | Inquiry |
| PMmRNL-0001 | EGFP mRNA-LNP | Inquiry |
| PMmRNL-0002 | mCherry mRNA-LNP | Inquiry |
| PMmRNL-0003 | Firefly Luciferase mRNA-LNP | Inquiry |
| PMmRNL-0004 | Cas9-HA mRNA-LNP | Inquiry |
| PMmRNL-0005 | EGFP mRNA (no modificaiton)-LNP | Inquiry |
| PMmRNL-0006 | mCherry mRNA (no modificaiton)-LNP | Inquiry |
| PMmRNL-0007 | Firefly Luciferase mRNA (no modificaiton)-LNP | Inquiry |
| PMmRNL-0008 | spCas9 mRNA (no modificaiton)-LNP | Inquiry |
| PMmRNL-0009 | spCas9 mRNA (N1-Me-Pseudo UTP modified)-LNP | Inquiry |
| PMmRNL-0010 | SARS COV-2 Spike Protein (Alpha Variant) mRNA-LNP | Inquiry |
In order to find a delivery mechanism that can bypass the liver, Dr. John Lewis of the University of Alberta and Dalhousie University virologist Roy Duncan have collaborated for decades. Duncan is famous for discovering a protein made by a unique fusogenic orthoreovirus that has the ability to fuse cells together.
By combining this fusion protein with modified lipid nanoparticles designed to transport therapeutics, they successfully designed a proteolipid vehicle (PLV) platform. The PLV platform utilizes fusion-associated small transmembrane (FAST) proteins derived from the non-enveloped fusogenic orthoreovirus. This platform avoids the liver, allowing treatments to be more effectively targeted to areas such as the brain and lungs. It is less toxic than current delivery platforms while also avoiding stimulating the immune system. This means it can be given repeatedly, which is critical for treating diseases that require continuous or multiple interventions. The relevant research results were recently published in the journal Cell in a paper titled "Safe and effective in vivo delivery of DNA and RNA using proteolipid vehicles."
Figure 1. Adding FAST protein to a lipid formulation increases mRNA and pDNA expression. (Brown D W, et al., 2024)
To demonstrate that the new platform can deliver genetic payloads without being intercepted by the liver, Lewis and his team constructed a gene therapy using a protein that helps muscle development and is normally associated with a particularly muscular breed of cattle called Belgian Blue cattle. When introduced into mice, not only did the platform avoid the liver, but the resulting genetically modified mice had twice the muscle mass of untreated mice. This approach could be used to treat debilitating conditions such as frailty and sarcopenia.
"This platform is a plug-and-play solution, so everyone developing new gene editing technologies and treating diseases other than the liver can use this platform to develop their drugs," said Lewis. Lewis and his team are first using the technology to develop a new COVID-19 vaccine that will enter Phase 2 clinical trials.
"Clinical trials for Stargardt's disease could begin within the next two years, and studies are already underway for cancer therapies. Beyond that, this technology could treat diseases such as muscular dystrophy, cystic fibrosis, Alzheimer's disease and Parkinson's disease," Lewis said. "It's conceivable that this technology could allow us to cure all of these terrible, debilitating, rare diseases."
The significance of this platform goes far beyond just an advancement in delivery technology. It represents a paradigm shift in the treatment of genetic diseases, with the potential to change the lives of millions of people affected by previously untreatable diseases.
Reference
Brown D W, et al. Safe and effective in vivo delivery of DNA and RNA using proteolipid vehicles. Cell, 2024, 187(19): 5357-5375. e24.