Research

Using Aptamers as Tunable Cancer Therapeutics

Traditional chemotherapy drugs cause numerous unwanted side effects due to drug accumulation in normal tissue; only a very small amount of the drug actually reaches the tumor. Recent advances to prevent chemotherapy accumulation in normal tissues have primarily relied on antibody drug conjugates (ADCs), in which highly toxic chemotherapeutics are conjugated to tumor-specific antibodies. These antibodies bind to receptors on tumor cells, more specifically delivering the chemotherapy drug to the tumor and keeping it away from non-target tissues. However, as biological products, antibodies must be produced by cell-based systems, are difficult to chemically modify with precision and require humanization for clinical use. Aptamers, small nucleic acid ligands, are an attractive alternative to therapeutic antibodies. Aptamers do not require humanization, are easily amenable to chemical synthesis and modification and maintain antibody-like affinities and specificities at a fraction of antibody size. We are selecting aptamers against different tumor targets and developing them into targeting ligands to deliver drugs specifically to tumors.

Using Aptamers to Deliver Other Oligonucleotide Therapeutics

Recently several different oligonucleotide drugs, primarily siRNA drugs and antisense oligonucleotide (ASO) drugs, have been clinically approved. Most of these drugs are conjugated to a sugar ligand (GalNAc) that targets liver cells and efficiently delivers the oligonucleotides to the liver. There currently aren’t efficient methods to deliver these oligonucleotide drugs to other organs. We’re exploring the use of aptamers specific for non-liver cell types to deliver these oligonucleotide drugs to other tissues.