Abstract
BackgroundGene therapy remains a significant challenge due to lots of barriers limiting the genetic manipulation technologies. As for non-viral delivery vectors, they often suffer insufficient performance due to inadequate cellular uptake and gene degradation in endosome or lysosome. The importance of overcoming these conserved intracellular barriers is increasing as the delivery of genetic cargo.ResultsA surface-functionalized non-viral vector involving the biomimetic mannitol moiety is initiated, which can control the cellular uptake and promote the caveolae-mediated pathway and intracellular trafficking, thus avoiding acidic and enzymatic lysosomal degradation of loaded gene internalized by clathrin-mediated pathway. Different degrees of mannitol moiety are anchored onto the surface of the nanoparticles to form bio-inspired non-viral vectors and CaP-MA-40 exhibits remarkably high stability, negligible toxicity, and significantly enhanced transgene expression both in vitro and in vivo.ConclusionsThis strategy highlights a paradigmatic approach to construct vectors that need precise intracellular delivery for innovative applications.
Highlights
Gene therapy remains a significant challenge due to lots of barriers limiting the genetic manipulation technologies
It has been confirmed that the cellular uptake pathways involved in traditional non-viral vectors include mainly the clathrin-mediated pathway, as well as the caveolaemediated pathway [15,16,17,18]
Through the coordination interaction between the phosphonate groups of the MA-AL and the C a2+ of the core, MA-AL was anchored onto the surface of the calcium phosphate (CaP) with different degrees to obtain the functionalized CaP-MA non-viral vectors
Summary
Gene therapy remains a significant challenge due to lots of barriers limiting the genetic manipulation technologies. As for non-viral delivery vectors, they often suffer insufficient performance due to inadequate cellular uptake and gene degradation in endosome or lysosome. As for the non-viral delivery vectors, they often suffer insufficient performance due to poor transfection efficiency, relatively high toxicity, inadequate cellular uptake and gene degradation. It has been confirmed that the cellular uptake pathways involved in traditional non-viral vectors include mainly the clathrin-mediated pathway, as well as the caveolaemediated pathway [15,16,17,18]. The endocytic vesicles internalized through the clathrin-mediated pathway are readily entrapped into endosome and transfer their cargoes to lysosome followed by enzymatic degradation (Fig. 1) [19, 20]. Controlling the cellular uptake and consequent intracellular fates may be a promising paradigm to improve the transgene efficiency of traditional non-viral delivery vectors
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
