Poly(β-amino ester) Nanoparticles Modified with a Rabies-Virus-Derived Peptide for the Delivery of ASCL1 across a 3D In Vitro Model of the Blood–Brain Barrier

Abstract:

Gene editing has emerged as a therapeutic approach to manipulate the genome for killing cancer cells, protecting healthy tissues, and improving immune response to a tumor. The gene editing tool achaete-scute family bHLH transcription factor 1 CRISPR guide RNA (ASCL1-gRNA) is known to restore neuronal lineage potential, promote terminal differentiation, and attenuate tumorigenicity in glioblastoma tumors. Here, we fabricated a polymeric nonviral carrier to encapsulate ASCL1-gRNA by electrostatic interactions and deliver it into glioblastoma cells across a 3D in vitro model of the blood–brain barrier (BBB). To mimic rabies virus (RV) neurotropism, gene-loaded poly(β-amino ester) nanoparticles are surface functionalized with a peptide derivative of rabies virus glycoprotein (RVG29). The capability of the obtained NPs, hereinafter referred to as RV-like NPs, to travel across the BBB, internalize into …

Año de publicación:

2023

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Fuente:

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