Custom RNA Nanoparticles

Customized Products

Select a ligand for targeting specific cancer cells and desired therapeutics moieties (miRNA, anti-miRNA, siRNA, or chemical drug). We will prepare the required RNA Nanoparticle with high quality and in large scale for in vitro and in vivo studies.

The thermodynamically stable 4WJ is the core structure of the multifunctional RNA nanoparticle. The structure has a Tm higher than 80°C and can keep undissociated at ultralow concentrations after being diluted as in blood circulation in vivo. This structure has been patented and licensed by ExonanoRNA for future drug development.

About RNA Nanoparticles

What are custom RNA nanoparticles?

Our RNA nanoparticles are homogeneous structures on the 10-40 nm scale assembled from three or more synthetic RNA oligonucleotides. The size range has been strategically chosen to obtain particles that are too large for effective renal clearance, yet small enough to prevent uptake by Kupffer cells. The result is a particle with elongated circulation times and a biodistribution profile optimized for targeted drug delivery.

Why use RNA nanoparticles?

Our platform is designed for bottom-up self-assembly of inhouse designed and produced oligonucleotide building blocks. This approach has allowed us to finely tune the shape of the RNA nanoparticle in the design stage and optimize its biodistribution profile specifically for the type of administration and tissue of interest. Owing to this programmability, RNA nanoparticles have been employed in a range of biomedical and nanomaterial applications.

What are the typical applications of custom RNA nanoparticles?

Our RNA nanoparticles have been used for a range of different applications. We present a brief list below, for a complete list please see relevant references here.

Suggested NanoRNA™ applications:

• Image cell binding of your aptamer/ligand in flow cytometry
• Image cell binding of your aptamer/ligand in confocal microscopy
• Image cell uptake and trafficking of your aptamer/ligand in confocal microscopy
• Image cell targeting on an IVIS system in in vivo models

Are RNA nanoparticles stable in vivo?

The in vivo properties of our RNA nanostructures have been optimized through the incorporation of chemical modifications at the 2’ ribose position. Incorporation of 2’Ome or 2’Fluoro modifications has been demonstrated to increase its enzymatic and thermodynamic stability. Functionalization of the 3’ and 5’ termini with small chemical ligands and aptamers introduces biologically active RNA features and cell-specific targeting capabilities. This has proven to be an effective way for delivering drug cargoes to specific cancer cells in vivo without accumulation of RNA nanoparticles in healthy organs.

Summary of RNA nanoparticle properties:

1. Negative charge - prevents nonspecific cell uptake
2. Solid-phase synthesis - provides defined structure and stoichiometry
3. Multi-valency - allows combination therapy and simultaneous targeting and detection
4. Targeted delivery - allows receptor-mediated endocytosis
5. Advantageous size - extends in vivo circulation
6. Chemically modified - increases half-life (5-12 hr compared to 15-45 min for siRNA)
7. No antibody induction - allows repeated treatment for chronic diseases
8. Favorable pharmacokinetic profile

How are custom RNA nanoparticles designed?

Our RNA nanoparticles are designed in a modular fashion which makes it easy to switch out individual modules and incorporate custom modalities. For this purpose, RNA nanoparticles are designed by selecting 1) a nanoparticle scaffold, 2) a targeting ligand, and 3) a therapeutic modality.

Nanoparticle Scaffold – The scaffold is the core of the particle that gives it its size and shape and determines its in vivo properties. Our scaffolds have been optimized for enzymatic and thermodynamic stability and biodistribution profiles making them ideal for drug delivery and cell targeting applications. RNA scaffolds are available in various shapes and sizes.

Targeting Module – Custom targeting ligands such as small chemical ligands or aptamers can be incorporated onto one of the modules during chemical synthesis or via bioconjugation to one of the termini. The high thermodynamic stability of the scaffold ensures correct folding and function of the aptamers.

Therapeutic Module – Small chemical molecules and RNA-based therapeutics such as siRNA, miRNA, antimiRNA and RNA aptamers can be conjugated to the scaffold as a therapeutic moiety. Our modular approach allows easy switching between therapeutic groups without modifying any of the other RNA Nanoparticle components which provides a convenient platform for comparative analysis of therapeutic activity in vivo.

RNA nanoparticle production and quality control

RNA nanoparticles are composed of three or more individual oligonucleotides. Each oligonucleotide is produced inhouse on a solid-phase synthesizer which allows us to incorporate custom aptamer sequences and internal or terminal chemical modifications for bioconjugation. Oligos are then PAGE purified before undergoing stringent quality control. RNA nanoparticles are assembled from their building blocks, purified, and assayed for endotoxins.