Integration of Cell-Penetrating Peptides with Rod-like Bionanoparticles: Virus-Inspired Gene-Silencing Technology.
Ye TianMengxue ZhouHaigang ShiSijia GaoGuocheng XieMeng ZhuMan WuJun ChenZhongwei NiuPublished in: Nano letters (2018)
Inspired by the high gene transfer efficiency of viral vectors and to avoid side effects, we present here a 1D rod-like gene-silencing vector based on a plant virus. By decorating the transacting activator of transduction (TAT) peptide on the exterior surface, the TAT-modified tobacco mosaic virus (TMV) achieves a tunable isoelectric point (from ∼3.5 to ∼9.6) depending on the TAT dose. In addition to enhanced cell internalization, this plant virus-based vector (TMV-TAT) acquired endo/lysosomal escape capacity without inducing lysosomal damage, resulting in both high efficiency and low cytotoxicity. By loading silencer green fluorescent protein (GFP) siRNA onto the TMV-TAT vector (siRNA@TMV-TAT) and interfering with GFP-expressing mouse epidermal stem cells (ESCs/GFP) in vitro, the proportion of GFP-positive cells could be knocked down to levels even lower than 15% at a concentration of ∼100% cell viability. Moreover, by interfering with GFP-expressing highly metastatic hepatocellular carcinoma (MHCC97-H/GFP) tumors in vivo, treatment with siRNA@TMV-TAT complexes for 10 days achieved a GFP-negative rate as high as 80.8%. This work combines the high efficiency of viral vectors and the safety of nonviral vectors and may provide a promising strategy for gene-silencing technology.
Keyphrases
- high efficiency
- stem cells
- sars cov
- cell therapy
- single cell
- cancer therapy
- small cell lung cancer
- squamous cell carcinoma
- induced apoptosis
- mesenchymal stem cells
- quantum dots
- cell cycle arrest
- drug delivery
- cell death
- amino acid
- combination therapy
- bone marrow
- binding protein
- endoplasmic reticulum stress
- disease virus
- genome wide identification