Researchers at Tel Aviv University have made significant strides in developing a targeted RNA therapy for inflammatory bowel diseases (IBD) using lipid nanoparticles (LNPs). Study professor Dan Peer, senior faculty at Tel Aviv University’s Shmunis School of Biomedicine and Cancer Research. In addition to research that takes creative approaches to encapsulating locked nucleic acid (LNA) molecules, there is a versatile new option for patients afflicted with these crippling diseases.
The LNPs were carefully produced in high-throughput microfluidic mixers, enabling the engineering of their structure and composition with a high level of control. The team synthesized nanoparticles that are only 50 nanometers in diameter. These minuscule particles are precisely engineered to encapsulate LNA molecules, which are known for their strength and defiance against susceptibility. This remarkable advancement may allow for dramatically reducing treatment dosages needed to produce therapeutic efficacy.
Breakthrough in LNA Research
Peer pointed to the importance of LNA molecules for translational research such as his.
“Our study focused on unique RNA molecules called LNA. Unlike most RNA molecules, LNA molecules are very stable and do not break down easily. Consequently, until about 10 years ago, they were thought to have great potential as genetic drugs. However, experiments in laboratory animals, as well as clinical trials in humans (in chronic liver inflammation), showed that very large amounts of LNA are needed to achieve therapeutic efficacy.” – Prof. Peer
Traditionally, the high dosage requirements for LNA-based therapies presented complexities that made their development difficult. It was costly to administer high doses of the unencumbered commodity. This approach usually resulted in extreme adverse reactions as the drug traveled throughout the body. This led many researchers to write off LNA drug development altogether. Professor Peer and his research team wanted to look at a more focused approach that would address these problems.
LNPs: A Game Changer for RNA Therapy
The advanced design of the LNPs used in this study has drastically changed the dosage need. For one, researchers now need only 30 times less than what prior studies needed. This ultimately saves money spent on treatment while lowering the chances of harmful side effects.
It’s been a 13-year journey for Professor Peer’s lab to develop their lipid library. This resource has been an important driver in the development of these LNPs. This library allowed researchers to systematically explore a variety of lipid formulations. First and foremost, this allowed them, for the first time, to develop nanoparticles that deliver LNA molecules exceptionally well.
Additionally, the study used Cryo-electron microscopy (CryoEM) imaging to demonstrate that the LNPs retained their structural integrity. This is a cherry on top that confirms their promise as a really robust delivery system for RNA therapies. This culmination of such innovative, cutting-edge techniques makes LNPs the top contender for treating IBD and other diseases.
Expanding Potential Applications
Although we’re just thinking about how to cure inflammatory bowel diseases, the potential applications of this work goes much further. When talking about the various health implications of non-communicable diseases, Professor Peer described the wider applications for LNPs.
“Our study paves the way to developing new LNA-based drugs for inflammatory bowel diseases, as well as a wide range of other diseases—including rare genetic disorders, vascular and heart diseases, and neurological diseases such as Parkinson’s and Huntington’s. So far, we have demonstrated that the new method is effective in chronic bowel inflammation in mice. We hope to proceed to clinical trials in humans in the near future.” – Prof. Peer
The preclinical trial results point to an exciting future for this novel therapy. With continuing validation and soon-to-launch clinical trials, LNPs have the potential to completely change the treatment landscape. They can help us be the essential answer for IBD and other complex health burdens.