The vascular endothelial growth factor receptor (VEGFR) is an important angiogenic target for cancer gene therapy. In this study, we designed an mRNA-cleaving oligodeoxynucleotide that targets the VEGF receptor 2 (VEGFR2) transcript (VEGFR2 DNAzyme). This DNAzyme was found to digest efficiently mRNA substrates of VEGFR2 in a concentration- and time-dependent manner. We also showed that the DNAzyme induces apoptosis and markedly inhibits endothelial cell growth compared with a disabled DNAzyme and untreated controls. In contrast, the DNAzyme did not inhibit the growth of MDA-MB-435 cells in vitro. The DNAzyme in complex with a nonviral carrier also significantly inhibited tumor growth in vivo. After the fourth injection, there was nearly a 75% reduction of tumor size in the DNAzyme-treated group compared with the saline-injected control group (P = 0.024). Marked cell death in the peripheral regions of the tumor accompanied by a reduction in blood vessel density is consistent with the antiangiogenic mechanism of the DNAzyme. This study indicates that DNAzymes, targeting angiogenic growth factors of tumors, show promise as antitumor agents.
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Chemistry
December 2024
Southwest University, school of chemistry and chemical enjineering, 2 Tiansheng Road, Beibei District, Chongqing, 400700, Chongqing, CHINA.
Currently, metal-organic frameworks (MOFs) with tunability and covalent organic frameworks (COFs) with high stability are promising nanomaterials for electrochemiluminescence (ECL), while Ru-based metal covalent organic frameworks (Ru-MCOFs) have rarely been reported. Herein, an ECL immunosensor based on a strong ECL-emitting Ru-MCOF was proposed for the sensitive detection of the cardiac troponin-I (cTnI). Imine-linked Ru-MCOF was prepared as an ECL emitter via solvothermal method using tris(4,4' -diamino-2,2' -bipyridine)ruthenium(II) (Ru(dbpy)32+) as a precursor.
View Article and Find Full Text PDFNat Commun
December 2024
Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT, 05405, USA.
8-oxoguanine (8-oxoG) is a common oxidative DNA lesion that causes G > T substitutions. Determinants of local and regional differences in 8-oxoG-induced mutability across genomes are currently unknown. Here, we show DNA oxidation induces G > T substitutions and insertion/deletion (INDEL) mutations in human cells and cancers.
View Article and Find Full Text PDFAnal Chem
December 2024
Key Laboratory of Dairy Science, Ministry of Education, College of Food Science, Northeast Agricultural University, Harbin 150030, China.
is one of the most dangerous and contagious foodborne pathogens, posing a significant threat to public health and food safety. In this study, we developed a click chemistry-based fluorescence biosensing platform for highly sensitive detection of () by integrating the -cleavage activity of CRISPR/Cas12a with the CLICK17-mediated copper(II)-dependent azide-alkyne cycloaddition (Cu(II)AAC) click reaction. Herein, CLICK-17 can provide binding sites for Cu ions and high redox stability for one or much catalytically vital Cu within its active sites, which facilitate the click reaction.
View Article and Find Full Text PDFBioinform Biol Insights
December 2024
Cellular Informatics Laboratory, Cluster for Pioneering Research (CPR), RIKEN, Saitama, Japan.
Transposable elements (TEs) or transposons are thought to play roles in animal physiological processes, such as germline, early embryonic, and brain development, as well as aging. However, their roles have not been systematically investigated through experimental studies. In this study, we created a catalog of genes directly involved in replication, excision, or integration of transposon-coding DNA, which we refer to as transposon DNA processing genes (TDPGs).
View Article and Find Full Text PDFMikrochim Acta
December 2024
Key Laboratory for Analytical Science of Food Safety and Biology, MOE, Fujian Provincial Key Laboratory of Analysis and Detection for Food Safety, College of Chemistry, Fuzhou University, Fuzhou, 350108, China.
A triple signal amplified electrochemical aptasensor for the detection of bisphenol A (BPA) was developed for the first time based on gold nanoparticles (AuNPs), hemin/G-quadruplex DNAzyme, and exonuclease I (Exo I) assisted amplification strategies. The BPA aptamer (Apt) hybridized with the capture probe (CP) was fixed on the gold electrode (GE) to form the double-stranded DNA (dsDNA) structure. When BPA was present, the Apt was detached from the GE surface by specific recognition between the BPA and Apt, forming BPA-Apt complexes in solution.
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