Abstract
Drugs with novel and versatile modes of action, such as therapeutic nucleic acids or proteins, open new possibilities for the precise therapy of different diseases. The most crucial limitation during the development of a therapeutic drug remains the safe and efficient intracellular delivery.
To overcome the hurdles and to realize the successful delivery of such new biopharmaceuticals, our laboratory has recently developed a sequence-defined, cationic oligomer platform based on solid-phase synthesis. These multifunctional oligomers have displayed efficient delivery of therapeutic RNA in vitro and in vivo. In this chapter, we provide a brief background on the special features and applications of these carrier systems as well as detailed protocols for the oligomer and polyplex synthesis and their evaluation.
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References
Duncan R (2003) The drawing era of polymer therapeutics. Nat Rev Drug Discov 2(5):347–360
Duncan R, Gaspar R (2011) Nanomedicine(s) under the microscope. Mol Pharm 8(6):2101–2141
Haag R, Kratz F (2006) Polymer therapeutics: concepts and applications. Angew Chem Int Ed 45:1198–1215
Schaffert D et al (2011) Solid-phase synthesis of sequence-defined T-, i-, and U-shape polymers for pDNA and siRNA delivery. Angew Chem Int Ed Engl 50:8986–8989
Frohlich T et al (2012) Structure-activity relationships of siRNA carriers based on sequence-defined oligo (ethane amino) amides. J Control Release 160:532–541
Troiber C et al (2013) Stabilizing effect of tyrosine trimers on pDNA and siRNA polyplexes. Biomaterials 34:1624–1633
Edinger D et al (2014) Gene silencing and antitumoral effects of Eg5 or Ran siRNA oligoaminoamide polyplexes. Drug Deliv Transl Res 4(1):84–95
Maier K, Wagner E (2012) Acid-labile traceless click linker for protein transduction. J Am Chem Soc 134(24):10169–10173
Lächelt U et al (2014) Synthetic polyglutamylation of dual-functional MTX ligands for enhanced combined cytotoxicity of poly(I:C) nanoplexes. Mol Pharm 11(8):2631–2639
Edinger D, Wagner E (2011) Bioresponsive polymers for the delivery of therapeutic nucleic acids. Wiley Interdiscip Rev Nanomed Nanobiotechnol 3:33–46
Copolovici DM, Langel K, Langel Ü (2014) Cell-penetrating peptides: design, synthesis, and applications. ACS Nano 8(3):1972–1994
Mechtler K, Wagner E (1997) Gene transfer mediated by influenza virus peptides: the role of peptide sequences. New J Chem 21:105–111
Meyer M et al (2008) Breathing life into polycations: functionalization with pH-responsive endosomolytic peptides and polyethylene glycol enables siRNA delivery. J Am Chem Soc 130:3272–3273
Meyer M et al (2009) Synthesis and biological evaluation of bioresponsive and endosomolytic siRNA-polymer conjugate. Mol Pharm 6:752–762
Wagner E (2012) Polymers for siRNA delivery: inspired by viruses to be targeted, dynamic, and precise. Acc Chem Res 45:1005–1013
Dohmen C et al (2012) Nanosized multifunctional polyplexes for receptor-mediated siRNA delivery. ACS Nano 6:5198–5208
Lächelt U et al (2014) Fine-tuning of proton sponges by precise diaminoethanes and histidines in pDNA polyplexes. Nanomedicine: NBM 10:35–44
Schaffert D, Badgujar N, Wagner E (2011) Novel Fmoc-polyamino acids for solid phase synthesis of defined polyamidoamines. Org Lett 13(7):1586–1589
Chan WC, White PD (2000) Fmoc solid phase peptide synthesis: a practical approach. Oxford University Press, Oxford
Troiber C et al (2013) Comparison of four different particle sizing methods for siRNA polyplex characterization. Eur J Pharm Biopharm 84:255–264
Acknowledgements
This work was supported by the DFG Cluster “Nanosystems Initiative Munich”. We thank Wolfgang Rödl and Miriam Höhn for technical support, and Olga Brück for skillful assistance.
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Weber, J., Lächelt, U., Wagner, E. (2015). Multifunctional Oligoaminoamides for the Receptor-Specific Delivery of Therapeutic RNA. In: Langel, Ü. (eds) Cell-Penetrating Peptides. Methods in Molecular Biology, vol 1324. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2806-4_25
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DOI: https://doi.org/10.1007/978-1-4939-2806-4_25
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-2805-7
Online ISBN: 978-1-4939-2806-4
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