Abstract 552: Harnessing the Versatility of PLGA Nanoparticles for Targeted Cre-Mediated Recombination

Abstract

The Cre/LoxP recombinase system has emerged as an important tool for the generation of conditional somatic mouse mutants. This method enables spatial control of gene activity in almost any tissue, providing new avenues for studying gene function and establishing animal models of human diseases. A major technical advance was the development of ligand-dependent Cre recombinases that are activated by tamoxifen. While this advance has paved the way for temporally-controlled developmental studies previously deemed impractical, the generation of tissue-specific transgenic mouse lines can be time-consuming and costly. Herein, we design a ‘smart’, biocompatible, and biodegradable nanoparticle system that can be actively targeted to specific cell types in vivo through surface conjugation of antibodies. We provide proof-of-principle for successful delivery of macromolecules and plasmid DNA. Importantly, we demonstrate that these ‘smart’, tamoxifen-loaded nanoparticles can be precisely targeted to cells of interest in vivo to bind and activate Cre recombinase, resulting in tissue-specific Cre activation. This system provides a simple, yet powerful approach to induce recombination in a ubiquitious Cre system for a time- and cost-effective strategy to generate new transgenic mouse lines.