Work

Dendrimer conjugates for light-activated delivery of antisense oligonucleotides

Year: 2015

Type: article

Abstract: Therapeutic oligonucleotides, such as splice switching ONs (SSOs), provide opportunities for treating serious, life-threatening diseases. However, the development of ONs as therapeutic agents has progressed slowly, because difficult cytosolic delivery of SSOs into the cytosol and nucleus remains a major barrier. Photochemical internalization (PCI), a promising strategy for endosomal escape, was introduced to disrupt the endosomal membrane using light and a photosensitizer. Here we constructed Poly(amido amine) (PAMAM) dendrimer conjugates to simultaneously deliver SSOs and photosensitizers into endo/lysosomal compartments. After photo-irradiation, considerable ONs were observed to diffuse into the cytosol and accumulate in the nucleus. Furthermore, the PCI mediated cytosolic delivery of SSOs effectively enhanced their nuclear splice switching activity.

Source: RSC Advances

DOI: 10.1039/c5ra04091d

Authors: Ahu Yuan, Yiqiao Hu, Xin Ming

Institutions: University of North Carolina at Chapel Hill, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University

Language: English

Topic: RNA Interference and Gene Delivery

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: China Scholarship Council, Akershus Universitetssykehus, National Institutes of Health, National Cancer Institute

Awards: G1192852400, Carolina Center of Cancer Nanotechnology Excellence, G2629428901, G6740482248, G7515590470