PhD defence

CRB1 gene therapy coming of age: Mechanistic insight and rAAV assays on mouse & human retinal organoid models

• T.M. Buck

Date

Wednesday 28 September 2022

Time

16:15 - 17:00

Location

Academy Building
Rapenburg 73
2311 GJ Leiden

Supervisor(s)

• Prof. G.P.M. Luyten

Summary

The thesis describes the generation and analysis of retintis pigmentosa(RP)-CRB1 knockout mouse and human retinas: mouse RP-CRB1 (chapter 2), human RP-CRB1 organoids (chapter 4 and 5). The data indicates that the human RP-CRB1 disease can be studied in mice and human organoids. Then, we show that rAAV-CRB gene supplementation therapy to Müller glial cells of the RP-CRB1 mouse retina can protect it from stress-induced vision loss, and that human CRB2 cDNA was superior to human CRB1 cDNA (chapter 2). We then developed an improved rAAV tropism assay on human donor eyes (chapter 3). This assay shows that rAAV5 can efficiently infect Müller glial cells and photoreceptors, the target cells of a RP-CRB1 gene therapy. Also, rAAV5 infection studies outperformed rAAV9 on human retinal organoids and human donor retinas (chapter 4). Thus, this thesis on both human and mouse models provides new insight into retinal degeneration and rAAV gene supplementation therapies.

PhD dissertations

Approximately one week after the defence, PhD dissertations by Leiden PhD students are available digitally through the Leiden Repository, that offers free access to these PhD dissertations. Please note that in some cases a dissertation may be under embargo temporarily and access to its full-text version will only be granted later.

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