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N掺杂石墨烯量子点作为mRNA和pDNA新型转染剂的简便合成

Facile Synthesis of N-Doped Graphene Quantum Dots as Novel Transfection Agents for mRNA and pDNA.

作者信息

Ahn Minchul, Song Jaekwang, Hong Byung Hee

机构信息

Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 08826, Korea.

BioGraphene Inc., Advanced Institute of Convergence Technology, Suwon 16229, Korea.

出版信息

Nanomaterials (Basel). 2021 Oct 23;11(11):2816. doi: 10.3390/nano11112816.

Abstract

In the wake of the coronavirus disease 2019 (COVID-19) pandemic, global pharmaceutical companies have developed vaccines for the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Some have adopted lipid nanoparticles (LNPs) or viral vectors to deliver the genes associated with the spike protein of SARS-CoV-2 for vaccination. This strategy of vaccination by delivering genes to express viral proteins has been successfully applied to the mRNA vaccines for COVID-19, and is also applicable to gene therapy. However, conventional transfection agents such as LNPs and viral vectors are not yet sufficient to satisfy the levels of safety, stability, and efficiency required for the clinical applications of gene therapy. In this study, we synthesized N-doped graphene quantum dots (NGQDs) for the transfection of various genes, including messenger ribonucleic acids (mRNAs) and plasmid deoxyribonucleic acids (pDNAs). The positively charged NGQDs successfully formed electrostatic complexes with negatively charged mRNAs and pDNAs, and resulted in the efficient delivery and transfection of the genes into target cells. The transfection efficiency of NGQDs is found to be comparable to that of commercially available LNPs. Considering their outstanding stability even at room temperature as well as their low toxicity, NGQDs are expected to be novel universal gene delivery platforms that can outperform LNPs and viral vectors.

摘要

在2019冠状病毒病(COVID-19)大流行之后,全球制药公司纷纷研发针对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的疫苗。一些公司采用脂质纳米颗粒(LNP)或病毒载体来递送与SARS-CoV-2刺突蛋白相关的基因以进行疫苗接种。这种通过递送基因来表达病毒蛋白的疫苗接种策略已成功应用于COVID-19的mRNA疫苗,并且也适用于基因治疗。然而,诸如LNP和病毒载体等传统转染试剂尚不足以满足基因治疗临床应用所需的安全性、稳定性和效率水平。在本研究中,我们合成了用于转染各种基因(包括信使核糖核酸(mRNA)和质粒脱氧核糖核酸(pDNA))的氮掺杂石墨烯量子点(NGQD)。带正电荷的NGQD成功地与带负电荷的mRNA和pDNA形成静电复合物,并导致基因有效地递送至靶细胞并实现转染。发现NGQD的转染效率与市售LNP相当。鉴于其即使在室温下也具有出色的稳定性以及低毒性,NGQD有望成为能够超越LNP和病毒载体的新型通用基因递送平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2adf/8620666/15ece91ef49b/nanomaterials-11-02816-g001.jpg

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