Deregulation of Circular RNAs in Cancer From the Perspectives of Aberrant Biogenesis, Transport and Removal.

CircRNAs (circular RNAs) are a class of RNAs generated from circularization with multiple novel functions. Recent studies have revealed the aberrant expression and aberrant functions of circRNAs in various tumors; thus, circRNAs have been recognized as promising cancer biomarkers. However, the underlying mechanisms behind their aberrant expression and functions remain unclear. In this review, we discuss at length the cancer-specific deregulation of circRNAs and the potential underlying aberrant events in circRNA biogenesis, localization and removal in cancer cells.

Partial DNA-guided Cas9 enables genome editing with reduced off-target activity.

CRISPR-Cas9 is a versatile RNA-guided genome editing tool. Here we demonstrate that partial replacement of RNA nucleotides with DNA nucleotides in CRISPR RNA (crRNA) enables efficient gene editing in human cells. This strategy of partial DNA replacement retains on-target activity when used with both crRNA and sgRNA, as well as with multiple guide sequences. Partial DNA replacement also works for crRNA of Cpf1, another CRISPR system. We find that partial DNA replacement in the guide sequence significantly reduces off-target genome editing through focused analysis of off-target cleavage, measurement of mismatch tolerance and genome-wide profiling of off-target sites. Using the structure of the Cas9-sgRNA complex as a guide, the majority of the 3' end of crRNA can be replaced with DNA nucleotide, and the 5 - and 3'-DNA-replaced crRNA enables efficient genome editing. Cas9 guided by a DNA-RNA chimera may provide a generalized strategy to reduce both the cost and the off-target genome editing in human cells.

Universal Multifunctional Nanoplatform Based on Target-Induced in Situ Promoting Au Seeds Growth to Quench Fluorescence of Upconversion Nanoparticles.

Construction of a new multifunctional chemo/biosensing platform for small biomolecules and tumor markers is of great importance in analytical chemistry. Herein, a novel universal multifunctional nanoplatform for biomolecules and enzyme activity detection was proposed based on fluorescence resonance energy transfer (FRET) between upconversion nanoparticles (UCNPs) and target-inducing enlarged gold nanoparticles (AuNPs). The reductive molecule such as H2O2 can act as the reductant to reduce HAuCl4, which will make the Au seeds grow. The enlarged AuNPs can effectively quench the fluorescence of UCNPs owing to the good spectral overlap between the absorption band of the AuNPs and the emission band of the UCNPs. Utilizing the FRET between the UCNPs and enlarged AuNPs, good linear relationship between the fluorescence of UCNPs and the concentration of H2O2 can be found. Based on this strategy, H2O2 related molecules such as l-lactate, glucose, and uric acid can also be quantified. On the basis of UCNPs and PVP/HAuCl4, a general strategy for other reductants such as ascorbic acid (AA), dopamine (DA), or enzyme activity can be established. Therefore, the universal multifunctional nanoplatform based on UCNPs and the target-inducing in situ enlarged Au NPs will show its potential as a simple method for the detection of some life related reductive molecules, enzyme substrates, as well as enzyme activity.

Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo.

The combination of Cas9, guide RNA and repair template DNA can induce precise gene editing and the correction of genetic diseases in adult mammals. However, clinical implementation of this technology requires safe and effective delivery of all of these components into the nuclei of the target tissue. Here, we combine lipid nanoparticle-mediated delivery of Cas9 mRNA with adeno-associated viruses encoding a sgRNA and a repair template to induce repair of a disease gene in adult animals. We applied our delivery strategy to a mouse model of human hereditary tyrosinemia and show that the treatment generated fumarylacetoacetate hydrolase (Fah)-positive hepatocytes by correcting the causative Fah-splicing mutation. Treatment rescued disease symptoms such as weight loss and liver damage. The efficiency of correction was >6% of hepatocytes after a single application, suggesting potential utility of Cas9-based therapeutic genome editing for a range of diseases.

Upconversion nanosensor for sensitive fluorescence detection of Sudan I-IV based on inner filter effect.

Sudan dyes are banned as food additives due to the carcinogenicity of their metabolites in the human body. Therefore, it is of great significance for sensitive detection of Sudan dyes. This paper reports a novel nanosensor for Sudan dyes detection based on fluorescence (FL) quenching of hexadecyl trimethyl ammonium bromide (CTAB) stabilized upconversion nanoparticles (UCNPs) through the inner filter effect (IFE). In the presence of Sudan I-IV, the fluorescence emission of UCNPs was effectively quenched due to the absorption bands of Sudan I-IV largely covered the emission bands of UCNPs. Under the optimized conditions, the FL was quenched with Sudan concentration over the range of 0.05-40, 0.01-20, 0.01-40 and 0.05-40 µg/mL for Sudan I-IV, respectively. The corresponding limit of detection is 15.1, 2.83, 3.52 and 16.7 ng/mL (at 3σ/slope) respectively. Meanwhile, the nanosensor shows good selectivity, sensitivity and can be successfully applied to detection of Sudan in chili powder samples.