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Genetic modification of mice without the need for extensive breeding

Per Svenningsen

Cardiovascular disease affects a large proportion of the population and may arrise because of changes in genes expressed in kidney and blood vessels. Genetically modified mice play a crucial role in understanding the underlying disease mechanisms and over the past 10 years, the use of genetically modified mice has increased by 40%. However, new figures have shown that 75% of the genetically modified mice produced by conventional methods are never directly involved in reserach, but instead they are only used to create and maintain the genetically modified mouse strains through extensive breeding programs. Therefore, there is enormous potential to reduce the number of mice used in research if we develope alternative methods to create genetically modified mice with no need for extensive breeding programs.

Gene modification can be created with adeno-associated vectors (AAV), which are virus-like particles comprising genetic DNA material surrounded by a protective protein coat. AVVs provide a safe and effective way to make gene modification in mice, but the current AAV-variants primarily target liver cells and therefore they cannot modify gene expression in kidney and blood vessels.

The AAV coat protein determines the target cells, and in this project, we will use a newly developed system to create new forms of AAV coat protein, and develope AAV-variants that can effectively deliver DNA material to cells kidney and blood vessels. With the novel AAV-variants, we will accomplish a deeper understanding of the mechanisms that underlie the developement of cardiovascular diseases while reducing the use of genetically modified mice.

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