in vitro facilitates transduction of cardiac specific tissue in vivo. We currently are examining whether the transduction process is energy independent as well as whether it involves endocytosis. Also, the size limitation for the cargo to be delivered is unknown, but presumably it is as large as or larger than the M13 phage used for the identification of the peptide. Given the fact that CTP-mediated transduction of cardiac tissue is efficient, specific and rapid, it could be used to deliver a variety of proteins, peptides, small molecules and viral and non-viral gene transfer vectors to the heart for treating cardiac conditions. In addition, it could be used diagnostically to determine the extent of References 1. Wiviott SD, Morrow DA, Frederick PD, Giugliano RP, Gibson CM, et al. (2004) Performance of the thrombolysis in myocardial infarction risk index in the National Registry of Myocardial Infarction-3 and -4: a simple index that predicts mortality in ST-segment elevation myocardial infarction. J Am Coll Cardiol 44: 783–9. 2. Rogers WJ, Canto JG, Lambrew CT, Tiefenbrunn AJ, Kinkaid B, et al. (2000) Temporal trends in the treatment of over 1.5 million patients with myocardial infarction in the US from 1990 through 1999: the National Registry of Myocardial Infarction 1, 2 and 3. J Am Coll Cardiol 36(7): 2056–63. 3. Pachori AS, Melo LG, Hart ML, Noiseux N, Zhang L, et al. (2004) Hypoxia- regulated therapeutic gene as a preemptive treatment strategy against ischemia/ reperfusion tissue injury. Proc Natl Acad Sci U S A 101(33): 12282–7. 4. Kawano S, Kubota T, Monden Y, Tsutsumi T, Inoue T, et al. (2006) Blockade of NF-kappaB improves cardiac function and survival after myocardial infarction. Am J Physiol Heart Circ Physiol 291(3): H1337–44. 5. Arap W, Pasqualini R, Ruoslahti E (1998) Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science 279(5349): 377–80. 6. Kolonin MG, Saha PK, Chan L, Pasqualini R, Arap W (2004) Reversal of obesity by targeted ablation of adipose tissue. Nat Med 10(6): 625–32. 7. Yao VJ, Ozawa MG, Trepel M, Arap W, McDonald DM, et al. (2005) Targeting pancreatic islets with phage display assisted by laser pressure catapult microdissection. Am J Pathol 166(2): 625–36. Identifying a Cardiac PTD viable cardiac tissue following infarct or ischemia reperfusion injury. Overall, the identification of a heart-specific delivery peptide should allow for novel biological treatments for cardiac conditions. Author Contributions Conceived and designed the experiments: MZ SMA NG SCW PDR. Performed the experiments: MZ BEP. Analyzed the data: MZ BEP SMA SCW PDR. Contributed reagents/materials/analysis tools: MZ BEP NG SCW PDR. Wrote the paper: MZ PDR. 8. Mi Z, Lu X, Mai JC, Ng BG, Wang G, et al. (2003) Identification of a synovial fibroblast-specific protein transduction domain for delivery of apoptotic agents to hyperplastic synovium. Mol Ther 8(2): 295–305. 9. Kelly KA, Nahrendorf M, Yu AM, Reynolds F, Weissleder R (2006) In vivo phage display selection yields atherosclerotic plaque targeted peptides for imaging. Mol Imaging Biol 8(4): 201–7. 10. Zhang L, Hoffman JA, Ruoslahti E (2005) Molecular profiling of heart endothelial cells. Circulation 112(11): 1601–11. 11. McGuire MJ, Samli KN, Johnston SA, Brown KC (2004) In vitro selection of a peptide with high selectivity for cardiomyocytes in vivo. J Mol Biol 342(1): 171–82. 12. Molenaar TJ, Michon I, de Haas SA, van Berkel TJ, Kuiper J (2002) Uptake and processing of modified bacteriophage M13 in mice: implications for phage display. Virology 293(1): 182–91. 13. Pasqualini R, Ruoslahti E (1996) Organ targeting in vivo using phage display peptide libraries. Nature 380(6572): 364–6. 14. Segvich SJ, Smith HC, Kohn DH (2009) The adsorption of preferential binding peptides to apatite-based materials. Biomaterials 30(7): 1287–98. 15. Hyun S, Lee EH, Park J, Yu J (2008) Tentacle type peptides as artificial lectins against sulfated Lewis X and A. Bioorg Med Chem Lett 18(14): 4011–4. PLoS ONE | www.plosone.org 11 August 2010 | Volume 5 | Issue 8 | e12252