Neuron‐specific delivery of nucleic acids mediated by Tet1‐modified poly(ethylenimine)

Abstract

Background-The development of minimally invasive, non-viral gene delivery vehicles for the central nervous system (CNS) is an important technology goal in the advancement of molecular therapies for neurological diseases. One approach is to deliver materials peripherally that are recognized and retrogradely transported by motor neurons toward the CNS. Tet1 is a peptide identified by Boulis and coworkers to possess the binding characteristics of tetanus toxin, which interacts specifically with motor neurons and undergoes fast, retrograde delivery to cell soma. In this work, Tet1-poly(ethylenimine) (Tet1-PEI) was synthesized and evaluated as a neurontargeted delivery vehicle.

Polymersomes, smaller than you think: ferrocene as a TEM probe to determine core structure

“…Small molecular weight hydrophobic molecules can be incorporated into the membrane (Ghoroghchian, et al, 2006b) and hydrophilic molecules encapsulated within the aqueous core (Lomas, et al, 2007). The polymersome can be surface-functionalized with groups that promote cellular uptake (Christian, et al, 2007;Roy, et al, 2010) or target specific cell types (Park, et al, 2007).…”

Gene and Cell Therapy for Peripheral Neuropathy

“…This peptide was identified based on its' homology to the tetanus toxin and it enhances neurotropism. This peptide was used by Park and colleagues to successfully target plasmid DNA the neural cells and DRG cells in vitro (Park, Lasiene et al 2007) and in vivo via an injection into lateral ventricle of mice. The tet-1 complexed plasmid was found to target adult neural progenitor cells (NPCs) (Kwon, Lasiene et al 2010).…”

Peptide-modified vectors for nucleic acid delivery to neurons

“…Tet1-PEI synthesis-Tet1-PEI was synthesized as described previously [22]. Briefly, branched polyethylenimine (PEI, MW 25k; Sigma, St. Louis, MO) was modified with 2 mole equivalents of N-succinimidyl 3-(2-pyridyldithio)-propionate (SPDP; Pierce, Rockford, IL) in DMF for 4 hours at room temperature.…”

“…This peptide was shown to be internalized and transported by neurons both in vitro and in vivo [31]. Park et al demonstrated that neuron association of nonviral gene delivery vehicles is significantly increased when the vectors are modified with Tet1 peptide [22]. Tet1 peptide bearing a C-terminal cysteine was covalently linked to PEI using disulfide chemistry at ~0.6 Tet1 peptides per PEI and polyplexes were formed with plasmid DNA.…”