Targeted axonal import (TAxI) peptide delivers functional proteins into spinal cord motor neurons after peripheral administration

Drew L. Sellers, Jamie M. Bergen, Russell N. Johnson, Heidi Back, John M. Ravits, Philip J. Horner, Suzie H. Pun

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

A significant unmet need in treating neurodegenerative disease is effective methods for delivery of biologic drugs, such as peptides, proteins, or nucleic acids into the central nervous system (CNS). To date, there are no operative technologies for the delivery of macromolecular drugs to the CNS via peripheral administration routes. Using an in vivo phage-display screen, we identify a peptide, targeted axonal import (TAxI), that enriched recombinant bacteriophage accumulation and delivered protein cargo into spinal cord motor neurons after intramuscular injection. In animals with transected peripheral nerve roots, TAxI delivery into motor neurons after peripheral administration was inhibited, suggesting a retrograde axonal transport mechanism for delivery into the CNS. Notably, TAxI-Cre recombinase fusion proteins induced selective recombination and tdTomato-reporter expression in motor neurons after intramuscular injections. Furthermore, TAxI peptide was shown to label motor neurons in the human tissue. The demonstration of a nonviral-mediated delivery of functional proteins into the spinal cord establishes the clinical potential of this technology for minimally invasive administration of CNS-targeted therapeutics.

Original languageEnglish (US)
Pages (from-to)2514-2519
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number9
DOIs
StatePublished - Mar 1 2016

Keywords

  • Drug delivery
  • Motor neuron
  • Peripheral nerve
  • Phage display

ASJC Scopus subject areas

  • General

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