Circular Single-Stranded DNA: Discovery, Biological Effects, and Applications.

The field of nucleic acid therapeutics has witnessed a significant surge in recent times, as evidenced by the increasing number of approved genetic drugs. However, current platform technologies containing plasmids, lipid nanoparticle-mRNAs, and adeno-associated virus vectors encounter various limitations and challenges. Thus, we are devoted to finding a novel nucleic acid vector and have directed our efforts toward investigating circular single-stranded DNA (CssDNA), an ancient form of nucleic acid. CssDNAs are ubiquitous, but generally ignored. Accumulating evidence suggests that CssDNAs possess exceptional properties as nucleic acid vectors, exhibiting great potential for clinical applications in genetic disorders, gene editing, and immune cell therapy. Here, we comprehensively review the discovery and biological effects of CssDNAs as well as their applications in the field of biomedical research for the first time. Undoubtedly, as an ancient form of DNA, CssDNA holds immense potential and promises novel insights for biomedical research.

Role of RNA m6A modification in titanium dioxide nanoparticle-induced acute pulmonary injury: An in vitro and in vivo study.

RNA N6-methyladenosine (m6A) modification regulates the cell stress response and homeostasis, but whether titanium dioxide nanoparticle (nTiO2)-induced acute pulmonary injury is associated with the m6A epitranscriptome and the underlying mechanisms remain unclear. Here, the potential association between m6A modification and the bioeffects of several engineered nanoparticles (nTiO2, nAg, nZnO, nFe2O3, and nCuO) were verified thorough in vitro experiments. nFe2O3, nZnO, and nTiO2 exposure significantly increased the global m6A level in A549 cells. Our study further revealed that nTiO2 can induce m6A-mediated acute pulmonary injury. Mechanistically, nTiO2 exposure promoted methyltransferase-like 3 (METTL3)-mediated m6A signal activation and thus mediated the inflammatory response and IL-8 release through the degeneration of anti-Mullerian hormone (AMH) and Mucin5B (MUC5B) mRNAs in a YTH m6A RNA-binding protein 2 (YTHDF2)-dependent manner. Moreover, nTiO2 exposure stabilized METTL3 protein by the lipid reactive oxygen species (ROS)-activated ERK1/2 pathway. The scavenging of ROS with ferrostatin-1 (Fer-1) alleviates the ERK1/2 activation, m6A upregulation, and the inflammatory response caused by nTiO2 both in vitro and in vivo. In conclusion, our study demonstrates that m6A is a potential intervention target for alleviating the adverse effects of nTiO2-induced acute pulmonary injury in vitro and in vivo, which has far-reaching implications for protecting human health and improving the sustainability of nanotechnology.

RNA m6A Modification Alteration by Black Phosphorus Quantum Dots Regulates Cell Ferroptosis: Implications for Nanotoxicological Assessment.

Nanosafety is a major concern for nanotechnology development. Evaluation of the transcriptome and the DNA methylome is proposed for nanosafety assessments. RNA m6A modification plays a crucial role in development, disease, and cell fate determination through regulating RNA stability and decay. Here, since black phosphorus quantum dots (BPQDs), among many other types of QDs, increase the global m6A level and decrease the demethylase ALKBH5 level in lung cells, the epitranscriptome is taken into consideration for the first time to evaluate nanosafety. Both the transcriptome and m6A epitranscriptome analyses show that BPQDs alter many biological processes, such as the response to selenium ions and the lipoxygenase pathway, indicating possible ferroptosis activation. The results further show that BPQDs cause lipid peroxidation, mitochondrial dysfunction, and iron overload. Recognition of these modified mRNAs by YTHDF2 leads to mRNAs' decay and eventually ferroptosis. This study shows that RNA m6A modification not only is a more sophisticated indicator for nanosafety assessment but also provides novel insight into the role of RNA m6A in regulating BPQD-induced ferroptosis, which may be broadly applicable to understanding the functions of RNA m6A under stress.