title: Circumventing Brain Barriers: Nanovehicles for Retroaxonal Therapeutic Delivery.
abstract: In addition to safeguarding the central nervous system (CNS) from the vast majority of pathogens and toxins, transvascular barriers impose immense challenges to the delivery of beneficial cargo. A few toxins and neurotropic viruses capable of penetrating the brain have proved to be potentially valuable for neuron targeting and enhanced transfer of restorative medicine and therapeutic genes. Here we review molecular concepts and implications of the highly neurotropic tetanus toxin (TeTx) and botulinum neurotoxins (BoNTs) and their ability to infiltrate and migrate throughout neurons. We discuss recent applications of their detoxified variants as versatile nanovehicles for retroaxonal delivery of therapeutics to motor neurons and synapses. Continued advances in research on these remarkable agents in preclinical trials might facilitate their future use for medical benefit.
authors.affiliation: Institute for Biological and Medical Imaging, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany; Munich School of Bioengineering, Technical University Munich, 81675 Munich, Germany; International Centre for Neurotherapeutics, Dublin City University, Dublin 9, Ireland. Electronic address: saak.ovsepian@gmail.com.
authors.forename: Saak V
authors.initials: SV
authors.lastname: Ovsepian
authors.affiliation: Institute of Radiation Biology, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.
authors.forename: Valerie B
authors.initials: VB
authors.lastname: O'Leary
authors.affiliation: Institute for Biological and Medical Imaging, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany; Munich School of Bioengineering, Technical University Munich, 81675 Munich, Germany.
authors.forename: Vasilis
authors.initials: V
authors.lastname: Ntziachristos
authors.affiliation: International Centre for Neurotherapeutics, Dublin City University, Dublin 9, Ireland.
authors.forename: J Oliver
authors.initials: JO
authors.lastname: Dolly
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D001905:Botulinum Toxins / Q000378:metabolism*; D002490:Central Nervous System / Q000378:metabolism*; D002491:Central Nervous System Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002493:Central Nervous System Diseases / Q000188:drug therapy / Q000378:metabolism; D004337:Drug Carriers / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D009046:Motor Neurons / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D013744:Tetanus Toxin / Q000378:metabolism*
chemical_list: D002491:Central Nervous System Agents; D004337:Drug Carriers; D013744:Tetanus Toxin; D001905:Botulinum Toxins