Prostate-specific Membrane Antigen (PSMA) Aptamers for Prostate Cancer Imaging and Therapy

Abstract

Current therapies for advanced-stage prostate cancer have shown limited efficacy due to the molecular complexity of this aggressive disease and the unwanted side effects that result from the treatments themselves. Chemotherapeutic drug cocktails are currently the preferred treatment option to inhibit multiple targets simultaneously, thereby reducing drug-resistance in advanced-stage disease. However, owing to the non-selective nature of these drugs, targeted approaches that eliminate toxicity to non-target tissues and reduce the amount of drug that needs to be administered to the patient are warranted. Prostate-specific membrane antigen (PSMA), a transmembrane receptor expressed on malignant prostate cancer cells, has been identified as a promising therapeutic target for targeted therapy of prostate cancer. PSMA-targeted agents have included small molecules, antibodies, and nucleic acid aptamers. This review focuses on oligonucleotide-based ligands (DNA and RNA aptamers) that target PSMA and their use in imaging and therapeutic applications for prostate cancer. This review covers important concepts pertaining to the clinical translation of PSMA aptamers (safety, stability, and pharmacokinetics) and highlight existing hurdles and future prospects.

Introduction and History of the Chemistry of Nucleic Acids Therapeutics

“…Most of the lessons learned in the development of chemistry in antisense field have facilitated the development of these approaches. In aptamers, modified nucleosides, such as 2 0 -O-methyl, 2 0 -fluoro or 2 0 -amino, and modified internucleotide linkages such as PS-linkages or boranophosphate are regularly employed [152,153]. In the case of mRNA therapy, considerations of use of chemical modifications are different than in other approaches.…”