NanoCore, a Core Facility of the Icahn Genomics Institute (IGI), focuses on the use of lipid nanoparticles and RNA-based approaches to develop new gene therapies.

Lipid Nanoparticles

Lipid nanoparticles (LNPs) are the most advanced non-viral gene delivery system used in the clinic. They are composed of a set of lipids that can encapsulate different class of RNA molecules in nanovescicles. Four components are generally critical for LNP formulations, which include an ionizable cationic lipid, a helper lipid, cholesterol, and a PEG-lipid. Briefly, ionizable cationic lipids are a key component; they interact with RNA and promote RNA endosomal escape in cells. Helper lipids and cholesterol promote formulation stability and delivery efficiency. PEG-lipid prevents particle aggregation and prolong circulation time in vivo.

To prepare LNPs, the lipids and RNA are dissolved separately in ethanol and acidic aqueous solution, respectively. Next, the two solutions are mixed with an automated microfluidic device. Then, ethanol is removed by dialysis. The final LNP/RNA formulation is characterized based on the percentage of RNA encapsulation, the diameter of the LNP, and the polydispersity index, which measure the heterogeneity of the LNP composition. These are all services provided at NanoCore. LNPs enhance the stability and delivery efficiency of mRNA, allowing customization for targeted applications, including vaccines or therapies for diverse diseases. This technology has been proven effective with the recent COVID-19 vaccines, which deliver mRNAs in vivo, thereby overcoming major barriers in genetic medicines.

RNA Therapeutics

RNA therapy is an emerging class of genetic medicine that uses the unique properties of RNA molecules to treat or prevent human diseases. RNA-based therapeutics include antisense oligonucleotides (ASOs), small interfering RNA (siRNA), microRNA (miRNA), RNA aptamers, and messenger RNA (mRNA). While ASOs, siRNA, and miRNA can theoretically target any cellular transcripts, mRNA therapeutics can be used to express functional proteins for vaccination, protein replacement therapy, and so on. RNA aptamers can directly bind specific receptors or inhibit protein activity similar to small molecule inhibitors and blocking antibody therapies. By acting on proteins, transcripts, and genes, RNA therapeutics tremendously expand the repertoire of druggable targets providing the foundations for the development of new therapeutic strategies.

RNA therapy possesses many advantages. For example, once the nucleic acid chemistry and the delivery method are established, the production of new and personalized RNA-based drugs can be achieved in a relatively short period using these pre-established methodologies. This rapid development process, as seen in the creation of the COVID-19 vaccines, minimizes the risk of genotoxicity. Overall, RNA therapy is rapidly emerging as one of the leading technologies in medicine with the potential to revolutionize the clinical outcomes of an endless number of diseases.