miRNA Delivery

RNA Nanoparticles for Cancer Inhibition Research

What is NanoRNA™

NanoRNA™ are RNA nanoparticles designed for cancer therapeutics research applications. This series of customizable RNA nanoparticles contains (a) a targeting ligand and (b) a therapeutic modality to assay the therapeutic efficacy of novel targeting or therapeutic modalities. These particles are ideal to test cell uptake, endosome release, and therapeutic efficacy of your therapeutic payload.

How do I use RNA Nanoparticles for inhibition studies?

Our RNA nanoparticles have been extensively tested as a platform to assay individual components in targeted drug delivery, such as targeting ligands, aptamer, siRNA, miRNA, antimiR, and small chemical drugs. Its in vivo properties, biodistribution, and pharmacokinetic profile are well studied and have been documented in many research studies and in vivo models. This wealth of information and comparative data on RNA nanoparticles is now available in the form of a platform assay to study in vitro and in vivo targeting capabilities of your novel chemical ligands or aptamers.

What are the applications of RNA Nanoparticles for inhibition studies?

Our RNA nanoparticles have been used for a range of different applications.
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

What are 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 as well as optimize their biodistribution profile specifically for the type of administration and tissue of interest. Because of this programmability, RNA nanoparticles have been employed in a range of biomedical and nanomaterial applications.

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 of delivering drug cargoes to specific cancer cells in vivo without any 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 the 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.

RNA Nanoparticles For In Vivo Inhibition

RNA Nanoparticles For In Vitro Inhibition