Highly selective transgene expression through the flip-excision switch system by using a unilateral spacer sequence.

ABSTRACT: The flip-excision switch (FLEX) system with an adeno-associated viral (AAV) vector allows expression of transgenes in specific cell populations having Cre recombinase. A significant issue with this system is non-specific expression of transgenes in tissues after vector injection. We show here that Cre-independent recombination events in the AAV genome carrying the FLEX sequence occur mainly during the production of viral vectors in packaging cells, which results in transgene expression in off-target populations. Introduction of a relatively longer nucleotide sequence between two recognition sites at the unilateral side of the transgene cassette, termed a unilateral spacer sequence (USS), is useful to suppress the recombination in the viral genome, leading to the protection of non-specific

SUBMITTER: Matsushita N 

PROVIDER: S-EPMC10014282 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature