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About the Authors:
Janeen H. Trembley
Affiliations Research Service, Minneapolis VA Health Care System, Minneapolis, Minnesota, United States of America, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, United States of America, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, United States of America
Gretchen M. Unger
Affiliation: GeneSegues Inc., Chaska, Minnesota, United States of America
Vicci L. Korman
Affiliation: GeneSegues Inc., Chaska, Minnesota, United States of America
Md. Joynal Abedin
Affiliations Research Service, Minneapolis VA Health Care System, Minneapolis, Minnesota, United States of America, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, United States of America
Lucas P. Nacusi
Affiliation: GeneSegues Inc., Chaska, Minnesota, United States of America
Rachel I. Vogel
Affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, United States of America
Joel W. Slaton
Affiliation: Department of Urology, University of Minnesota, Minneapolis, Minnesota, United States of America
Betsy T. Kren
Affiliations Research Service, Minneapolis VA Health Care System, Minneapolis, Minnesota, United States of America, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, United States of America, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America
Khalil Ahmed
* E-mail: [email protected]
Affiliations Research Service, Minneapolis VA Health Care System, Minneapolis, Minnesota, United States of America, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, United States of America, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, United States of America, Department of Urology, University of Minnesota, Minneapolis, Minnesota, United States of America
Introduction
Across the spectrum of malignant disease, effective therapy for advanced and/or metastatic cancer remains a critical goal in efforts to reduce cancer-related mortality. Nucleic acid-based cancer therapy continues to hold significant promise for gene-specific, effective, and low-toxicity disease treatment which has the additional potential of overcoming therapeutic resistance frequently observed in aggressive disease. Both antisense and siRNA-based therapeutics have entered into clinical trials with very moderate success [1]–[4]. Key considerations for the systemic use of short linear nucleic acids as a therapeutic moiety include that they are directed specifically to tumor cells in a protected manner, effectively cross cell membranes and engage the cell machinery. Numerous approaches incorporating these concepts have demonstrated utility in mouse models including, e.g., PSMA-targeted aptamer-siRNA chimeras, Her2-targeted single chain fragmented antibody-protamine fusion protein...