Title:
DEVELOPMENT AND CHARACTERIZATION OF VIRAL VECTORS FOR STRESS-DEPENDENT TRANSGENE EXPRESSION IN NEURONS

dc.contributor.advisor Gross, Robert E.
dc.contributor.author Santiago-Lopez, Angel J.
dc.contributor.committeeMember LaPlaca, Michelle
dc.contributor.committeeMember Prausnitz, Mark
dc.contributor.committeeMember Kane, Ravi
dc.contributor.committeeMember Lee, Jae-Kyung
dc.contributor.department Chemical and Biomolecular Engineering
dc.date.accessioned 2022-05-18T19:19:55Z
dc.date.available 2022-05-18T19:19:55Z
dc.date.created 2021-05
dc.date.issued 2021-01-19
dc.date.submitted May 2021
dc.date.updated 2022-05-18T19:19:55Z
dc.description.abstract This work introduces a viral vector that captures intrinsic signals associated with the unfolded protein response (UPR) to control gene product delivery in neurons. The development of this molecular tool responds to the need for physiologically responsive gene therapy constructs to prevent unwanted side effects associated with transgene overexpression. Additionally, when used as a reporter assay, this tool addresses a basic research need for the kinetic monitoring of cellular stress and proteostasis dysfunction in neurons. To address these needs, we designed a viral-based ATF4 reporter comprising 384 bp of the initial coding region, including the 5’UTR of human ATF4 as a translational control operator fused to an enhanced green fluorescent protein (EGFP). For biological characterization, we conducted extensive time-lapse fluorescent microscopy assays in several in vitro models of proteostasis dysfunction, including ER stress, proteasome inactivation, phosphatase inhibition, and alpha-synuclein overexpression. Collectively, our results demonstrate the feasibility of mobilizing cellular stress signaling to create physiologically-responsive viral vectors for use in neuroscience.
dc.description.degree Ph.D.
dc.format.mimetype application/pdf
dc.identifier.uri http://hdl.handle.net/1853/66406
dc.language.iso en_US
dc.publisher Georgia Institute of Technology
dc.subject Unfolded protein response
dc.subject Neurons
dc.subject Neurodegeneration
dc.title DEVELOPMENT AND CHARACTERIZATION OF VIRAL VECTORS FOR STRESS-DEPENDENT TRANSGENE EXPRESSION IN NEURONS
dc.type Text
dc.type.genre Dissertation
dspace.entity.type Publication
local.contributor.advisor Gross, Robert E.
local.contributor.corporatename School of Chemical and Biomolecular Engineering
local.contributor.corporatename College of Engineering
relation.isAdvisorOfPublication 89002865-712a-460d-b3f2-d6fa13e129fd
relation.isOrgUnitOfPublication 6cfa2dc6-c5bf-4f6b-99a2-57105d8f7a6f
relation.isOrgUnitOfPublication 7c022d60-21d5-497c-b552-95e489a06569
thesis.degree.level Doctoral
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