Acoustically targeted measurement of transgene expression in the brain
| dc.contributor.advisor | Szablowski, Jerzy | en_US |
| dc.creator | Seo, Joon Pyung | en_US |
| dc.date.accessioned | 2025-05-30T21:38:48Z | en_US |
| dc.date.created | 2025-05 | en_US |
| dc.date.issued | 2025-04-25 | en_US |
| dc.date.submitted | May 2025 | en_US |
| dc.date.updated | 2025-05-30T21:38:48Z | en_US |
| dc.description.abstract | Gene expression is a critical component of brain physiology and activity. Brain development, function, and plasticity relies on a regulated process of converting genetic information into functional products. However, monitoring gene expression in the living brain has been a significant challenge. The confined structure of the brain, protected by the cranium and shielded by the blood-brain barrier, has posed difficulty in non-invasive and sensitive measurement of gene expression with specificity. The aim of this thesis is to develop a new paradigm of technology capable of measuring gene expression in the brain non-invasively with cell-type, spatial, and temporal specificity. To achieve this, we combined focused ultrasound liquid biopsy and recovery of engineered protein markers that are designed to be expressed in neurons and exit into the brain’s interstitium. When ultrasound is applied to targeted brain regions, it temporarily opens the blood-brain barrier and releases the interstitial markers into the bloodstream. Once in blood, the markers can be readily detected from blood collection followed by compatible biochemical techniques. We call this Recovery of Markers through InSonation (REMIS). We demonstrated improved recovery of engineered Gaussia luciferase marker, under constitutive promoter, from the brain into the blood in every tested animal. Further, we implemented the markers to measure endogenous neuronal signaling activity by controlling the expression of the marker under a genetic circuit that responds to c-Fos when activated by enhanced neuronal activity. Lastly, we measured enhanced serum level of overexpressed human alpha-synuclein in the engineered Parkinson’s disease model mThy1-aSyn (Line61) mouse strain with REMIS. Overall, our work demonstrates the feasibility of combining engineered gene expression reporters and focused ultrasound liquid biopsy to noninvasively and specifically measure gene expression in the intact brain. | en_US |
| dc.embargo.lift | 2026-05-01 | en_US |
| dc.embargo.terms | 2026-05-01 | en_US |
| dc.format.mimetype | application/pdf | en_US |
| dc.identifier.uri | https://hdl.handle.net/1911/118540 | en_US |
| dc.language.iso | en | en_US |
| dc.subject | REMIS | en_US |
| dc.title | Acoustically targeted measurement of transgene expression in the brain | en_US |
| dc.type | Thesis | en_US |
| dc.type.material | Text | en_US |
| thesis.degree.department | Applied Physics | en_US |
| thesis.degree.discipline | Applied Physics/Bioengineering | en_US |
| thesis.degree.grantor | Rice University | en_US |
| thesis.degree.level | Doctoral | en_US |
| thesis.degree.name | Doctor of Philosophy | en_US |