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Tissue-Specific Delivery of Oligonucleotides

  • Xin Xia
  • Nicolette Pollock
  • Jiehua Zhou
  • John RossiEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 2036)

Abstract

From the initial discovery of short-interfering RNA (siRNA) and antisense oligonucleotides for specific gene knockdown at the posttranscriptional level to the current CRISPR-Cas9 system offering gene editing at the genomic level, oligonucleotides, in addition to their biological functions in storing and conveying genetic information, provide the most prominent solutions to targeted gene therapies. Nonetheless, looking into the future of curing cancer and acute diseases, researchers are only cautiously optimistic as the cellular delivery of these polyanionic biomacromolecules is still the biggest hurdle for their therapeutic realization. To overcome the delivery obstacle, oligonucleotides have been encapsulated within or conjugated with delivery vehicles for enhanced membrane penetration, improved payload, and tissue-specific delivery. Such delivery systems include but not limited to virus-based vehicles, gold-nanoparticle vehicles, formulated liposomes, and synthetic polymers. In this chapter, delivery challenges imposed by biological barriers are briefly discussed; followed by recent advances in tissue-specific oligonucleotide delivery utilizing both viral and nonviral delivery vectors, discussing their advantages, and how judicious design and formulation could improve and expand their potential as delivery vehicles.

Key words

Oligonucleotide therapeutics Tissue-specific Phagocytosis EPR Endosomal escape Ligands Antibodies Aptamers 

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Xin Xia
    • 1
  • Nicolette Pollock
    • 1
  • Jiehua Zhou
    • 1
  • John Rossi
    • 1
    Email author
  1. 1.Department of Molecular and Cellular BiologyBeckman Research InstituteCity of Hope, DuarteUSA

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