Abstract

Virus Like Particles (VLPs) are self-assembling protein subunits which organize in vitro into hollow protein cages that mimic the structure of a viral capsid. VLPs possess valuable characteristics of the native virus including immunogenicity and a propensity for entrance into cells. However, they lack the viral genome and the ability to replicate, rendering them non-virulent. VLPs can be internally and externally modified utilizing genetic engineering and biochemical techniques. Applications of modified VLPs are vast in nanomedicine, and tissue-specific drug targeting is a desirable potential use for this technology. VLP HK97 is a well characterized VLP derived from a bacteriophage found in E.coli and has yet to be tested in the zebrafish model. Experiments show unmodified VLP HK97 is non-toxic at biologically relevant doses in zebrafish, making this particle a viable option for further study with the addition of cell penetrating peptides (CPPs). The addition of RGD onto the external surface of VLP HK97, a cell targeting peptide known to target integrin receptors, drastically decreased the amount of VLP tolerated by the zebrafish. Further localization experiments reveal that this may be due to increased localization into distinct cell subtypes in the zebrafish embryo. The modified particle also showed localization to known sites of integrin expression in larval zebrafish. These experiments conclude that VLP HK97 is a viable candidate as a drug delivery platform. VLP HK97 is a viable platform for testing cell-specific targeting for drugs and other molecules in a wide variety of zebrafish disease models.

Date of publication

Spring 4-16-2019

Document Type

Thesis

Language

english

Persistent identifier

http://hdl.handle.net/10950/1306

Committee members

Dr. Brent R. Bill, Dr. Ali Azghani, Dr. Dustin Patterson

Degree

Biology

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