Targeted delivery using aptamers

Presenter: Donald H. Burke/David Porciani, University of Missouri, USA

Date: July 25, 2019

Description:
Currently, effective cell-targeted delivery tools for oligonucleotide therapeutics are limited. Aptamers that internalize into target cells have been shown to deliver a wide variety of nucleic acid therapeutics, from siRNAs (<15 kDa, 19-21 nt/strand) to large, functional RNA payloads (50-80 kDa, 175-250 nt). In this webinar we will discuss the options for linking aptamers to the therapeutic nucleic acid, what to watch out for during this process and how to best confirm specific targeting.

• General introduction
  Toward the Selection of Cell Targeting Aptamers with Extended Biological Functionalities to Facilitate Endosomal Escape of Cargoes.
  Tawiah KD, Porciani D, Burke DH.
  Biomedicines. 2017 Aug 24;5(3). pii: E51.
• FACS-SELEX
  Enrichment of cell-targeting and population-specific aptamers by fluorescence-activated cell sorting.
  Raddatz MS, Dolf A, Endl E, Knolle P, Famulok M, Mayer G.
  Angew Chem Int Ed Engl. 2008;47(28):5190-3.
• Waz aptamer
  A New Transferrin Receptor Aptamer Inhibits New World Hemorrhagic Fever Mammarenavirus Entry.
  Maier KE, Jangra RK, Shieh KR, Cureton DK, Xiao H, Snapp EL, Whelan SP, Chandran K, Levy M.
  Mol Ther Nucleic Acids. 2016 May 24;5:e321.
• C10.36 aptamer
  Modular Assembly of Cell-targeting Devices Based on an Uncommon G-quadruplex Aptamer.
  Opazo F, Eiden L, Hansen L, Rohrbach F, Wengel J, Kjems J, Mayer G.
  Mol Ther Nucleic Acids. 2015 Sep 1;4:e251.Translocation of a Cell Surface Spliceosomal Complex Induces Alternative Splicing Events and Lymphoma Cell Necrosis.
  Tonapi SS, Pannu V, Duncan JE, Rosenow M, Helmstetter A, Magee D, Zhang Q, Tinder TT, Richards M, Halbert DD, Famulok M, Spetzler D, Miglarese MR, O’Neill HA, Mayer G.
  Cell Chem Biol. 2019 May 16;26(5):756-764.e6.
• Dye labelling of aptamers/complex formation
  Modular cell-internalizing aptamer nanostructure enables targeted delivery of large functional RNAs in cancer cell lines.
  Porciani D, Cardwell LN, Tawiah KD, Alam KK, Lange MJ, Daniels MA, Burke DH.
  Nat Commun. 2018 Jun 11;9(1):2283.
• Formation of aptamer-payload complex
  A Fluorescent Split Aptamer for Visualizing RNA-RNA Assembly In Vivo.
  Alam KK, Tawiah KD, Lichte MF, Porciani D, Burke DH.
  ACS Synth Biol. 2017 Sep 15;6(9):1710-1721.
• Guidelines for aptamer research
  Aptamer-Mediated Delivery and Cell-Targeting Aptamers: Room for Improvement.
  Yan AC, Levy M.
  Nucleic Acid Ther. 2018 Jun;28(3):194-199.
• Cell binding and uptake of the nucleolin binding aptamer (AS1411) is nucleolin-independent, and only its antiproliferative effect depends on nucleolin
  A new paradigm for aptamer therapeutic AS1411 action: uptake by macropinocytosis and its stimulation by a nucleolin-dependent mechanism.
  Reyes-Reyes EM, Teng Y, Bates PJ.
  Cancer Res. 2010 Nov 1;70(21):8617-29.
• Other references
  Two interconvertible folds modulate the activity of a DNA aptamer against transferrin receptor.
  Porciani D, Signore G, Marchetti L, Mereghetti P, Nifosì R, Beltram F.
  Mol Ther Nucleic Acids. 2014 Jan 28;3:e144.Aptamer-based endocytosis of a lysosomal enzyme.
  Chen CH, Dellamaggiore KR, Ouellette CP, Sedano CD, Lizadjohry M, Chernis GA, Gonzales M, Baltasar FE, Fan AL, Myerowitz R, Neufeld EF.
  Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15908-13.

  Inhibition of cell proliferation by an anti-EGFR aptamer.
  Li N, Nguyen HH, Byrom M, Ellington AD.
  PLoS One. 2011;6(6):e20299.

  Staining of cell surface human CD4 with 2′-F-pyrimidine-containing RNA aptamers for flow cytometry.
  Davis KA, Lin Y, Abrams B, Jayasena SD.
  Nucleic Acids Res. 1998 Sep 1;26(17):3915-24.

David Porciani, PhD, is a Post-Doc with Prof. Burke at the University of Missouri School of Medicine. His scientific interests have focused on the selective recognition of tumor cell-surface markers, aiming to discriminate malignant cells from healthy cells. He gained his PhD in the development of aptamer nanocarriers as tools for targeted drug delivery from the Scuola Normale Superiore, Pisa, Italy, in 2016 and has published several high profile papers on this subject.

Prof. Donald H. Burke is the Associate Chair of Department for Molecular Microbiology & Immunology at the University of Missouri School of Medicine. He obtained a Ph.D. in biophysical chemistry and microbial genetics from the University of California, Berkeley in 1992 and trained as a Post-Doc in RNA biochemistry and aptamer selection with Larry Gold at the University of Colorado, Boulder.
Dr. Burke’s research is focused on these questions: 1) What can nucleic acids do? 2) How do their sequences and structures relate to their ability to do it? and 3) Can we engineer new biologies by expressing artificial RNAs in cells?