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Targeted Therapeutics

3DNA-based Therapeutics

Genisphere's 3DNA is a unique nanotechnology ideally suited for targeted drug delivery. The DNA architecture enables the flexible and rapid attachment of therapeutic payloads and targeting molecules. 3DNA is inherently versatile and easily adaptable to applications including targeted small molecules, bispecific antibodies, nucleic acid delivery, and antibody-drug conjugates.

3DNA based therapeutics

For a given disease, a therapeutic molecule and targeting molecule are selected and formulated with 3DNA. This 3DNA formulation would then be administered systemically to the patient, via injection. The targeting molecule directs the 3DNA and its active drug molecule to the disease site. The 3DNA and therapeutic molecule are internalized by the cells at the site of disease. The targeted disease cell is either killed, or biologically modified, based on the therapeutic compound administered using the 3DNA platform.

Specific Targeting

Targeting can be achieved by attaching specific antibodies, antibody fragments, peptides, sugars, or small molecules (vitamins, carbohydrates, lipids, bioactive molecules) to short DNA oligos which are hybridized to 3DNA. Since 3DNA is multivalent, two or more unique targeting devices may be used to deliver with the same nanocarrier. Pre-clinical data have demonstrated biodistribution profiles are determined by the chosen targeting moiety. Specific targeting molecules allow 3DNA transport across the blood-brain barrier and other physiological barriers to accumulate in targeted regions.

Folic Acid 3DNA Biodistribution

Therapeutic Payloads

A variety of chemistries can be used to load therapeutic molecules onto the core 3DNA nanocarrier. Therapeutic antibodies and peptides can bind via an oligonucleotide linker that bridges the antibody or peptide to the 3DNA scaffold. Simple hybridization can be used to deliver siRNA, mRNA, and plasmid DNA using 3DNA. Small molecule therapeutics can be conjugated to DNA using linkers which degrade or reverse upon cellular internalization. The multivalent properties of 3DNA enable the delivery of multiple therapeutic molecules that may be the same or different. For example, several of the same small drug may be bound to a single 3DNA or two different bioactive antibodies, peptides, or small molecules may be delivered to modulate or amplify a therapeutic response. In oncology applications, 3DNA-based therapeutics have shown specific targeting of tumors, selective killing of targeted cells, and tumor shrinkage (result below generated in collaboration with Dr. Janet Sawicki at the Lankenau Institute for Medical Research).

Ovarian tumor efficacy doxorubicin 3DNA