An RNA alternative to human transferrin: A new tool for targeting human cells

Samantha E. Wilner, Brian Wengerter, Keith Maier, Maria De Lourdes Borba Magalhães, David Soriano Del Amo, Supriya Pai, Felipe Opazo, Silvio O. Rizzoli, Amy Yan, Matthew Levy

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

The transferrin receptor, CD71, is an attractive target for drug development because of its high expression on a number of cancer cell lines and the blood brain barrier. To generate serum-stabilized aptamers that recognize the human transferrin receptor, we have modified the traditional aptamer selection protocol by employing a functional selection step that enriches for RNA molecules which bind the target receptor and are internalized by cells. Selected aptamers were specific for the human receptor, rapidly endocytosed by cells and shared a common core structure. A minimized variant was found to compete with the natural ligand, transferrin, for receptor binding and cell uptake, but performed ~twofold better than it in competition experiments. Using this molecule, we generated aptamer-targeted siRNA-laden liposomes. Aptamer targeting enhanced both uptake and target gene knockdown in cells grown in culture when compared to nonmodified or nontargeted liposomes. The aptamer should prove useful as a surrogate for transferrin in many applications including cell imaging and targeted drug delivery.

Original languageEnglish (US)
Article numbere21
JournalMolecular Therapy - Nucleic Acids
Volume1
DOIs
StatePublished - 2012

Fingerprint

Transferrin
Transferrin Receptors
RNA
Liposomes
Gene Knockdown Techniques
Endocytosis
Blood-Brain Barrier
Pharmaceutical Preparations
Small Interfering RNA
Ligands
Cell Line
Serum
Neoplasms

Keywords

  • Aftamer
  • Liposome
  • SiRNA
  • SNALPs
  • Transferrin

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Wilner, S. E., Wengerter, B., Maier, K., Borba Magalhães, M. D. L., Del Amo, D. S., Pai, S., ... Levy, M. (2012). An RNA alternative to human transferrin: A new tool for targeting human cells. Molecular Therapy - Nucleic Acids, 1, [e21]. https://doi.org/10.1038/mtna.2012.14

An RNA alternative to human transferrin : A new tool for targeting human cells. / Wilner, Samantha E.; Wengerter, Brian; Maier, Keith; Borba Magalhães, Maria De Lourdes; Del Amo, David Soriano; Pai, Supriya; Opazo, Felipe; Rizzoli, Silvio O.; Yan, Amy; Levy, Matthew.

In: Molecular Therapy - Nucleic Acids, Vol. 1, e21, 2012.

Research output: Contribution to journalArticle

Wilner, SE, Wengerter, B, Maier, K, Borba Magalhães, MDL, Del Amo, DS, Pai, S, Opazo, F, Rizzoli, SO, Yan, A & Levy, M 2012, 'An RNA alternative to human transferrin: A new tool for targeting human cells', Molecular Therapy - Nucleic Acids, vol. 1, e21. https://doi.org/10.1038/mtna.2012.14
Wilner, Samantha E. ; Wengerter, Brian ; Maier, Keith ; Borba Magalhães, Maria De Lourdes ; Del Amo, David Soriano ; Pai, Supriya ; Opazo, Felipe ; Rizzoli, Silvio O. ; Yan, Amy ; Levy, Matthew. / An RNA alternative to human transferrin : A new tool for targeting human cells. In: Molecular Therapy - Nucleic Acids. 2012 ; Vol. 1.
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