Honors College Thesis


Assessing an Adult Zebrafish Model for In Vivo Delivery of Morpholino Oligomers Public Deposited

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  • Antisense morpholino oligomers are synthetic macromolecules can modify gene expression. While these compounds have great potential to treat a broad range of human diseases, they suffer from poor cellular delivery. Conjugating cell-penetrating peptides onto these morpholinos is one option of addressing delivery, however development remains slow due to the cost of the animal models used to assess in vivo delivery and safety of peptide-conjugated morpholinos. We have produced a novel transgenic zebrafish model that express gene transcripts for blue fluorescent protein. If the morpholino can successfully enter the nuclei, transcripts for red fluorescent proteins will also be expressed. Through retro-orbital injection, it was found that a particular cell-penetrating peptide was able to deliver a morpholino to zebrafish heart by a transcription-detecting assay. The results demonstrate that this zebrafish model has potential to be used an alternative vertebrate model to identify effective yet safe peptide-conjugated morpholinos for future pharmaceutical applications. Key Words: Morpholino, PMO, peptide-conjugated morpholino, PPMO, zebrafish, gene transcription, exon-skipping, BFP, RFP.
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