Our Science: Overview

Our targeted non-viral 3DNA® delivery platform is poised to transform the field of genetic medicines

The unique features of our proprietary 3DNA delivery platform can be applied to gene therapy, RNAi, and potentially gene-editing.

Multivalency

The 3DNA scaffold is a multivalent structure to which targeting molecules and nucleic acid based therapeutics can be attached. This property enables rapid optimization of both binding avidity and therapeutic potency and modularity, with high specificity of targeting. Ultimately, the 3DNA platform expands options for delivering multiple modalities, potentially including gene-editing.

Unparalleled Tissue & Cell Targeting Specificity

Our 3DNA delivery strategy improves cellular targeting and helps minimize off-target toxicities through a dual targeting approach. First, targeting molecules, such as antibodies, peptides or small molecules, which bind to cell surface proteins expressed on the target cells, are attached to the 3DNA platform. After binding to the target cell, the 3DNA scaffold and cargo are internalized into the cells of interest via a receptor-mediated process. By exploiting and withstanding the endocytotic process, the platform delivers gene sequences from outside the cell into the cytoplasm and cell nucleus. The dual targeting process is complete once a tissue specific promoter drives the expression of the delivered gene construct, minimizing off-target cell expression. In addition, our proprietary 3DNA scaffold enables high tissue specificity outside the liver with improved bioavailability, which results in reduced dose and low toxicity.

Delivery of Large Gene Constructs

Our proprietary 3DNA platform is capable of efficient delivery of genes to cells, eliminating the size constraints imposed by a number of viral vector technologies. The 3DNA scaffold has demonstrated the ability to deliver genes approaching 10kb, and we have yet to reach the upper limit for gene size that can be delivered. This means that we may be able to treat diseases that are currently untreatable.

Reduced Immunogenicity/Potential to Re-dose

The 3DNA scaffold has been designed to eliminate sequence specific elements that trigger immune responses such as those initiated by toll-like receptors (TLR’s). This may allow for the ability to re-dose genetic medicines. Repeat dosing studies, in multiple species, have no produced neutralizing antibodies to the 3DNA scaffold. Extensive preclinical data has demonstrated targeting, safety and efficacy of the novel 3DNA delivery platform.

Rapid Formulation Development

Manufacturing of the 3DNA scaffold is simple, reproducible, and scalable. The 3DNA scaffold can be made in bulk, stored, and used in a modular process for formulating genetic medicines. Generating a final genetic medicine using the 3DNA platform is a relatively straightforward process of taking the “off the shelf” 3DNA scaffold, attaching the relevant targeting molecules, and the nucleic acid based therapeutics.

The 3DNA platform has shown efficacy in animal models targeting multiple cell types including brain microglia, lung endothelial cells, B cells, T cells, eye myofibroblasts, liver, muscle, pancreas, as well as various tumor cells. Discovery research is ongoing or planned in the ear, heart, and kidney.

In dose escalation and chronic dosing studies, 3DNA has demonstrated no toxicity either at the cell level or at the tissue/macro level. In preclinical safety studies, formulations combining the 3DNA vector with both targeting molecules as well as therapeutic cargo have demonstrated strong safety profiles.

The platform has demonstrated rapid and efficient biodistribution, in many cases accumulating in the cells of interest within minutes after intravenous injection.