Modulating Human Tyrosine Hydroxylase Expression Through Control of Specific G-Quadruplex Formation
AssigneeKent State University
InventorsSoumitra BASU, Nathan BEALS, Mohamed M. FARHATH, Prakash KHAREL
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Abstract
Novel DNA molecule-based compositions and methods for delivery to target cells provide modulation of target G-quadruplex formation in the tyrosine hydroxylase (TH) promoter and allow for enhancement or repressing of specific G-quadruplexes that in turn regulate tyrosine hydroxylase transcription and catecholamine production, specifically dopamine. Use of the DNA-molecule-based compositions in treatment of neurological diseases and disorders is facilitated through a nanoparticle-based delivery system.
Claims14
A method for controlling dopamine production in the treatment of neurological disorders, comprising the steps of:
- a. providing an exogenous agent to regulate tyrosine hydroxylase (TH) expression in the catecholamine biogenesis pathway;
- and
- b. incorporating the exogenous agent into a nanoparticle drug delivery system to deliver the agent to a dopaminergic neuron via targeting with a TrkB peptide aptamer, wherein the exogenous agent is a DNA-based molecule comprising an engineered G-quadruplex (GQ)-targeting DNA clip that is complementary to and targets a segment of the TH49 sequence of human tyrosine hydroxylase promoter.
An engineered G-quadruplex (GQ)-targeting DNA clip, complementary to a segment of TH49 sequence of human TH promoter, for modulating tyrosine hydroxylase expression, comprising:
- a 5′GQ DNA clip or a 3′GQ DNA clip in combination with a polyethylene glycol (PEG)-coated gold nanoparticle (AuNP) as a central tethering agent, PEGylated tyrosine receptor kinase B (TrkB), and transferrin receptor 1 (Tfr1) aptamers.
A 5′GQ Clip nanoparticle, comprising:
- a 5′GQ clip molecule, a polyethylene glycol (PEG)-coated gold nanoparticle (AuNP) as a central tethering agent, PEGylated tyrosine receptor kinase B (TrkB), and transferrin receptor 1 (Tfr1) aptamers.
Dependencies are inferred from the claim text.