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dc.contributor.advisorIrvine, Darrell J
dc.contributor.advisorDenkin, Steven M
dc.contributor.authorLiang, Simon Jun Jie
dc.date.accessioned2021-05-21T09:21:14Z
dc.date.created2021
dc.date.issued2021-05-14
dc.date.submitted2021
dc.identifier.citationLiang, Simon Jun Jie. 2021. Designing self-amplifying replicons for transient gene expression of interleukin-18. Master's thesis, Harvard University Division of Continuing Education.
dc.identifier.other28411833
dc.identifier.urihttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37367606*
dc.description.abstractRNA-based therapeutics are on the rise as a re-emerging technology bolstered by the SARS-CoV-2 pandemic. However, issues such as storage, protein expression, and delivery are major challenges for the broad applicability. To address this issue, non-viral RNA replicon delivery systems can induce transient gene expression of immunomodulators and open the door to numerous potential targets that were once not viable due to dose-limiting toxicities affecting safety and efficacy. To that end, this work targets IL-18, a pleiotropic proinflammatory cytokine, which has been primarily viewed as a prognostic marker of various diseases like atherosclerosis, arthritis, diabetes, and cancer. In combination with another cytokine (IL-12), IL-18 is capable of enhancing the production of IFN-γ critical for anti-tumor immune responses. First, the synthesis of RNA replicons through in vitro transcription, characterization, and validation of IL-18 RNA replicons is described. Next, IL-18 RNA replicons are encapsulated in lipid nanoparticles and their function is analyzed using a melanoma cell line. Lastly, evidence of synergy between RNA replicons encoding for both IL-18 and IL-12 is shown through the production of robust IFN-γ responses in B16F10 co-cultures with naïve splenocytes. These studies provide a fundamental understanding to observe transient gene expression and synergy of dual expressing cytokines. Lastly, this system has the potential to be a promising tool for cancer immunotherapy.
dc.format.mimetypeapplication/pdf
dc.language.isoen
dash.licenseLAA
dc.subjectCancer immunotherapy
dc.subjectGene therapy
dc.subjectRNA delivery
dc.subjectSynthetic biology
dc.subjectBioengineering
dc.subjectNanotechnology
dc.titleDesigning self-amplifying replicons for transient gene expression of interleukin-18
dc.typeThesis or Dissertation
dash.depositing.authorLiang, Simon Jun Jie
dc.date.available2021-05-21T09:21:14Z
thesis.degree.date2021
thesis.degree.grantorHarvard University Division of Continuing Education
thesis.degree.levelMasters
thesis.degree.nameALM
dc.type.materialtext
thesis.degree.departmentExtension Studies
dc.identifier.orcid0000-0002-6109-7008
dash.author.emailliangs@uchicago.edu


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