justin.dassie@gmail.com
Mentor: Paloma Giangrande, Ph.D.
Lab Room: 5235 MERF
Lab Phone: 319-384-3243

Utilization of Aptamer Chimeras for Targeted Cancer Therapeutics

The goal of the Giangrande lab is to develop safer, more effective treatments for targeting certain types of cancer. In order to achieve this goal, potential therapies must be capable of targeted delivery to cancer cells and must also have a mechanism to induce cancer cell death. One such reagent which has both of these characteristics is an aptamer chimera. Aptamers are single stranded structured oligonucleotides which are proficient in binding their targets with high affinity and specificity. They are also capable of being generated to almost any target utilizing a process termed SELEX (Systematic Evolution of Ligands by EXponential enrichment). In our lab we utilize this technology to synthesize aptamers specific for extracellular receptors which are preferentially expressed/upregulated on cancer cells versus normal epithelia. Once generated, the aptamer can subsequently be conjugated to an siRNA molecule which targets a pro-survival gene necessary for cancer cell survival. Upon knock-down of the pro-survival gene, apoptosis of targeted cells ensues. These reagents can therefore be created to not only specifically target cancer cells, but also result in their death.



Thiel WH, Bair T, Peek AS, Liu X, Dassie J, Stockdale KR, Behlke MA, Miller FJ Jr, Giangrande PH. Rapid identification of cell-specific, internalizing RNA aptamers with bioinformatics analyses of a cell-based aptamer selection. PLoS One. 2012;7(9):e43836. Epub 2012 Sep 4. PubMed PMID: 22962591; PubMed Central PMCID: PMC3433472.

Thiel KW, Hernandez LI, Dassie JP, Thiel WH, Liu X, Stockdale KR, Rothman AM, Hernandez FJ, McNamara JO 2nd, Giangrande PH. Delivery of chemo-sensitizing siRNAs to HER2+-breast cancer cells using RNA aptamers. Nucleic Acids Res. 2012 Jul;40(13):6319-37. Epub 2012 Mar 30. PubMed PMID: 22467215; PubMed Central PMCID: PMC3401474.

Thiel WH, Bair T, Wyatt Thiel K, Dassie JP, Rockey WM, Howell CA, Liu XY, Dupuy AJ, Huang L, Owczarzy R, Behlke MA, McNamara JO, Giangrande PH. Nucleotide bias observed with a short SELEX RNA aptamer library. Nucleic Acid Ther. 2011 Aug;21(4):253-63. Epub 2011 Jun 28. PubMed PMID: 21793789; PubMed Central PMCID: PMC3198618.

Dassie JP, Liu XY, Thomas GS, Whitaker RM, Thiel KW, Stockdale KR, Meyerholz DK, McCaffrey AP, McNamara JO 2nd, Giangrande PH. Systemic administration of optimized aptamer-siRNA chimeras promotes regression of PSMA-expressing tumors. Nat Biotechnol. 2009 Sep;27(9):839-49. Epub 2009 Aug 23. PubMed PMID: 19701187; PubMed Central PMCID: PMC2791695.

Honors and Awards

• University of Iowa Presidential Fellowship
• Supported by the T32 Training Grant in Molecular & Cellular Biology