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The delivery of drugs into the central nervous system is limited by the blood–brain barrier.
In this paper, a screen of recombinant bacteriophage identified a peptide, targeted axonal import (TAx I), that is able to deliver protein cargo into spinal cord motor neurons after intramuscular injection by a retrograde transport mechanism.
The demonstration of a nonviral-mediated delivery system demonstrates the clinical potential of this technology to develop powerful therapeutic tools to treat motor neuron diseases.
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.
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Using an in vivo phage-display screen, we identify a peptide, targeted axonal import (TAx I), that enriched recombinant bacteriophage accumulation and delivered protein cargo into spinal cord motor neurons after intramuscular injection.
In animals with transected peripheral nerve roots, TAx I delivery into motor neurons after peripheral administration was inhibited, suggesting a retrograde axonal transport mechanism for delivery into the CNS.
Notably, TAx I-Cre recombinase fusion proteins induced selective recombination and td Tomato-reporter expression in motor neurons after intramuscular injections.