Recovery of Markers through Insonation: An alternative to monitoring gene expression in deep tissues
| dc.contributor.advisor | Szablowski, Jerzy | en_US |
| dc.creator | Seo, Joon Pyung | en_US |
| dc.date.accessioned | 2023-05-24T20:43:32Z | en_US |
| dc.date.created | 2022-12 | en_US |
| dc.date.issued | 2023-02-13 | en_US |
| dc.date.submitted | December 2022 | en_US |
| dc.date.updated | 2023-05-24T20:43:32Z | en_US |
| dc.description.abstract | We developed a method to noninvasively measure transgene expression in the specific brain regions using a blood test. To achieve this, we used engineered protein reporters that are released from the cells into the brain interstitium. We then used focused ultrasound (FUS) to transiently open the blood-brain barrier (BBBO) and release these reporters into the blood. We call this approach REcovery of Markers through InSonation, or REMIS. We show that levels of markers secreted from neurons into the serum correlate with the levels of transgene expression in the brain. We measured up to 5.5-fold increase of marker levels in the blood after opening of 8% of the blood-brain barrier (BBB). We show the procedure is well tolerated and avoids significant tissue damage, consistent with other BBB opening studies. Finally, we show that the marker is released from the brain over prolonged periods of time. The levels of the released marker were comparable at 7.5 minutes and 2 hours after FUS-BBBO (p=0.31, paired t-test). At the same time, the serum half-life of the marker injected intravenously was 7.6 minutes. This suggests that the marker was released from the brain gradually, replenishing the marker in the serum over 2 hours, and indicating a broad time window available for marker collection. Monitoring gene expression in deep tissues of living animals is critical for in vivo studies and translation of gene therapies. This technology allows for site-specific measurement of gene expression in the brain. | en_US |
| dc.embargo.lift | 2023-12-01 | en_US |
| dc.embargo.terms | 2023-12-01 | en_US |
| dc.format.mimetype | application/pdf | en_US |
| dc.identifier.citation | Seo, Joon Pyung. "Recovery of Markers through Insonation: An alternative to monitoring gene expression in deep tissues." (2023) Master’s Thesis, Rice University. <a href="https://hdl.handle.net/1911/114886">https://hdl.handle.net/1911/114886</a>. | en_US |
| dc.identifier.uri | https://hdl.handle.net/1911/114886 | en_US |
| dc.language.iso | eng | en_US |
| dc.rights | Copyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder. | en_US |
| dc.subject | Gene expression monitoring | en_US |
| dc.subject | Focused ultrasound | en_US |
| dc.subject | Blood-brain barrier | en_US |
| dc.title | Recovery of Markers through Insonation: An alternative to monitoring gene expression in deep tissues | en_US |
| dc.type | Thesis | en_US |
| dc.type.material | Text | en_US |
| thesis.degree.department | Applied Physics | en_US |
| thesis.degree.discipline | Engineering | en_US |
| thesis.degree.grantor | Rice University | en_US |
| thesis.degree.level | Masters | en_US |
| thesis.degree.name | Master of Science | en_US |
Files
Original bundle
1 - 1 of 1