Cell-internalization SELEX: method for identifying cell-internalizing RNA aptamers for delivering siRNAs to target cells.

Journal Article (Journal Article)

After a decade of work to address cellular uptake, the principal obstacle to RNAi-based therapeutics, there is now well-deserved, renewed optimism about RNAi-based drugs. Phase I and II studies have shown safe, strong, and durable-gene knockdown (80-90%, lasting for a month after a single injection) and/or clinical benefit in treating several liver pathologies. Although promising, these studies have also highlighted the need for robust delivery techniques to develop RNAi therapeutics for treating other organ systems and diseases. Conjugation of siRNAs to cell-specific, synthetic RNA ligands (aptamers) is being proposed as a viable solution to this problem. While encouraging, the extended use of RNA aptamers as a delivery tool for siRNAs awaits the identification of RNA aptamer sequences capable of targeting and entering the cytoplasm of many different cell types. We describe a cell-based selection process for the rapid identification and characterization of RNA aptamers suited for delivering siRNA drugs into the cytoplasm of target cells. This process, termed "cell-internalization SELEX (Systematic Evolution of Ligands by Exponential Enrichment)," entails the combination of multiple sophisticated technologies, including cell culture-based SELEX procedures, next-generation sequencing (NGS), and novel bioinformatics tools.

Full Text

Duke Authors

Cited Authors

  • Thiel, WH; Thiel, KW; Flenker, KS; Bair, T; Dupuy, AJ; McNamara, JO; Miller, FJ; Giangrande, PH

Published Date

  • 2015

Published In

Volume / Issue

  • 1218 /

Start / End Page

  • 187 - 199

PubMed ID

  • 25319652

Pubmed Central ID

  • PMC4435695

Electronic International Standard Serial Number (EISSN)

  • 1940-6029

Digital Object Identifier (DOI)

  • 10.1007/978-1-4939-1538-5_11


  • eng

Conference Location

  • United States