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

Research output: Contribution to journalArticle

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

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

PMID: 26888285

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Targeted axonal import (TAxI) peptide delivers functional proteins into spinal cord motor neurons after peripheral administration. / Sellers, Drew L.; Bergen, Jamie M.; Johnson, Russell N.; Back, Heidi; Ravits, John M.; Horner, Philip J.; Pun, Suzie H.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, No. 9, 01.03.2016, p. 2514-2519.

Research output: Contribution to journalArticle

Harvard

Sellers, DL, Bergen, JM, Johnson, RN, Back, H, Ravits, JM, Horner, PJ & Pun, SH 2016, 'Targeted axonal import (TAxI) peptide delivers functional proteins into spinal cord motor neurons after peripheral administration' Proceedings of the National Academy of Sciences of the United States of America, vol. 113, no. 9, pp. 2514-2519. https://doi.org/10.1073/pnas.1515526113

APA

Sellers, D. L., Bergen, J. M., Johnson, R. N., Back, H., Ravits, J. M., Horner, P. J., & Pun, S. H. (2016). Targeted axonal import (TAxI) peptide delivers functional proteins into spinal cord motor neurons after peripheral administration. Proceedings of the National Academy of Sciences of the United States of America, 113(9), 2514-2519. https://doi.org/10.1073/pnas.1515526113

Vancouver

Sellers DL, Bergen JM, Johnson RN, Back H, Ravits JM, Horner PJ et al. Targeted axonal import (TAxI) peptide delivers functional proteins into spinal cord motor neurons after peripheral administration. Proceedings of the National Academy of Sciences of the United States of America. 2016 Mar 1;113(9):2514-2519. https://doi.org/10.1073/pnas.1515526113

Author

Sellers, Drew L. ; Bergen, Jamie M. ; Johnson, Russell N. ; Back, Heidi ; Ravits, John M. ; Horner, Philip J. ; Pun, Suzie H. / Targeted axonal import (TAxI) peptide delivers functional proteins into spinal cord motor neurons after peripheral administration. In: Proceedings of the National Academy of Sciences of the United States of America. 2016 ; Vol. 113, No. 9. pp. 2514-2519.

BibTeX

@article{b2d57fef403449e6afbcf35dc75b4a61,
title = "Targeted axonal import (TAxI) peptide delivers functional proteins into spinal cord motor neurons after peripheral administration",
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.",
keywords = "Drug delivery, Motor neuron, Peripheral nerve, Phage display",
author = "Sellers, {Drew L.} and Bergen, {Jamie M.} and Johnson, {Russell N.} and Heidi Back and Ravits, {John M.} and Horner, {Philip J.} and Pun, {Suzie H.}",
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RIS

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T1 - Targeted axonal import (TAxI) peptide delivers functional proteins into spinal cord motor neurons after peripheral administration

AU - Sellers, Drew L.

AU - Bergen, Jamie M.

AU - Johnson, Russell N.

AU - Back, Heidi

AU - Ravits, John M.

AU - Horner, Philip J.

AU - Pun, Suzie H.

PY - 2016/3/1

Y1 - 2016/3/1

N2 - 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.

AB - 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.

KW - Drug delivery

KW - Motor neuron

KW - Peripheral nerve

KW - Phage display

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U2 - 10.1073/pnas.1515526113

DO - 10.1073/pnas.1515526113

M3 - Article

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SP - 2514

EP - 2519

JO - Proceedings of the National Academy of Sciences of the United States of America

T2 - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

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