Advances in RNAi therapeutic delivery to leukocytes using lipid nanoparticles

Srinivas Ramishetti, Dalit Landesman-Milo, Dan Peer

Research output: Contribution to journalReview article

19 Scopus citations

Abstract

Small interfering RNAs (siRNAs) therapeutics has advanced into clinical trials for liver diseases and solid tumors, but remain a challenge for manipulating leukocytes fate due to lack of specificity and safety issues. Leukocytes ingest pathogens and defend the body through a complex network. They are also involved in the pathogeneses of inflammation, viral infection, autoimmunity and cancers. Modulating gene expression in leukocytes using siRNAs holds great promise to treat leukocyte-mediated diseases. Leukocytes are notoriously hard to transduce with siRNAs and are spread throughout the body often located deep in tissues, therefore developing an efficient systemic delivery strategy is still a challenge. Here, we discuss recent advances in siRNA delivery to leukocyte subsets such as macrophages, monocytes, dendritic cells and lymphocytes. We focus mainly on lipid-based nanoparticles (LNPs) comprised of new generation of ionizable lipids and their ability to deliver siRNA to primary or malignant leukocytes in a targeted manner. Special emphasis is made on LNPs targeted to subsets of leukocytes and we detail a novel microfluidic mixing technology that could aid in changing the landscape of process development of LNPs from a lab tool to a potential novel therapeutic modality.

Original languageEnglish (US)
Pages (from-to)780-786
Number of pages7
JournalJournal of Drug Targeting
Volume24
Issue number9
DOIs
StatePublished - Oct 20 2016

Keywords

  • Ionizable lipids
  • leukocytes
  • lipid nanoparticles
  • microfluidic mixing
  • siRNA

ASJC Scopus subject areas

  • Pharmaceutical Science

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