In Vivo Use of a Multi-DNA Aptamer-Based Payload/Targeting System To Study Dopamine Dysregulation in the Central Nervous System

ACS Chemical Neuroscience
Erin M McConnellMaria C DeRosa

Abstract

The delivery of therapeutics across the blood-brain barrier remains a considerable challenge in investigating central nervous system related processes. In this work, a liposome vehicle was surface-modified with an aptamer that binds to the transferrin receptor and was loaded with two different dopamine-binding aptamer payloads. This system was effectively used to promote the delivery of the aptamer cargo from the peripheral injection site into the brain. The effect of these delivered aptamers on behavior was investigated in vivo in a locomotor task. The first dopamine binding aptamer assessed was a DNA aptamer, the binding of which had been previously validated through the aptamer-based biosensor development reported by several independent research groups. The second aptamer investigated was the result of a novel in vitro selection experiment described herein. Our data suggest that systemic administration of the modified liposomes led to delivery of the dopamine aptamers into the brain. Fluorescence microscopy revealed differential distribution of fluorescence based on the presence or absence of the transferrin receptor aptamer on the surface of fluorescently modified liposomes. In a behavioral experiment using cocaine administ...Continue Reading

Citations

Nov 6, 2018·Genes·Carla Lucia EspositoVittorio de Franciscis
Aug 4, 2019·Progress in Neurobiology·Kasper Bendix JohnsenTorben Moos
May 29, 2021·Biosensors & Bioelectronics·Yuqian ZhangAli K Yetisen
Jun 20, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Sarah ShigdarVittorio de Franciscis

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