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Although genetic factors contribute to almost half of all deafness cases, treatment options for genetic deafness are limited1–5. We developed a genome editing approach to target a dominantly inherited form of genetic deafness. Here we show that cationic lipid-mediated in vivo delivery of Cas9:guide RNA complexes can ameliorate hearing loss in a mouse model of human genetic deafness. We designed and validated in vitro and in primary fibroblasts genome editing agents that preferentially disrupt the dominant deafness-associated allele in the Tmc1 (transmembrane channel-like 1) Beethoven (Bth) mouse model, even though the mutant Bth allele differs from the wild-type allele at only a single base pair. Injection of Cas9:guide RNA:lipid complexes targeting the Bth allele into the cochlea of neonatal Bth/+ mice substantially reduced progressive hearing loss. We observed higher hair cell survival rates and lower auditory brainstem response (ABR) thresholds in injected ears compared with uninjected ears or ears injected with complexes that target an unrelated gene. Enhanced acoustic reflex responses were observed among injected compared to uninjected Bth/+ animals. These findings suggest protein:RNA complex delivery of target gene-disrupting agents in vivo as a potential strategy for the treatment of some autosomal dominant hearing loss diseases.

Clustered regularly interspaced short palindromic repeat-CRISPR-associated protein (CRISPR-Cas) systems, found in nature as microbial adaptive immune systems, have been repurposed into an important tool in biological engineering and genome editing, providing a programmable platform for precision gene targeting. These tools have immense promise as therapeutics that could potentially correct disease-causing mutations. However, CRISPR-Cas gene editing components must be transported directly to the nucleus of targeted cells to exert a therapeutic effect. Thus, efficient methods of delivery will be critical to the success of therapeutic genome editing applications. Here, we review current strategies available for in vivo delivery of CRISPR-Cas gene editing components and outline challenges that need to be addressed before this powerful tool can be deployed in the clinic.

Reported here is the first highly selective conversion of various waste plastics into C2 fuels under simulated natural environment conditions by a sequential photoinduced C−C cleavage and coupling pathway, where single‐use bags, disposable food containers, food wrap films, and their main components of polyethylene, polypropylene, and polyvinyl chloride can be photocatalytically transformed into CH3COOH without using sacrificial agents. As an example, polyethylene is photodegraded 100 % into CO2 within 40 h by single‐unit‐cell thick Nb2O5 layers, while the produced CO2 is further photoreduced to CH3COOH. Various methods and experiments disclose that O2 and .OH radicals trigger the oxidative C−C cleavage of polyethylene to form CO2, while other investigations show that the yielded CH3COOH stems from CO2 photoreduction by C−C coupling of .COOH intermediates. This two‐step plastic‐to‐fuel conversion may help to simultaneously address the white pollution crisis and harvest highly valuable multicarbon fuels in natural environments.

Antimicrobial resistance poses serious public health concerns and antibiotic misuse/abuse further complicates the situation; thus, it remains a considerable challenge to optimize/improve the usage of currently available drugs. We report a general strategy to construct a bacterial strain-selective delivery system for antibiotics based on responsive polymeric vesicles. In response to enzymes including penicillin G amidase (PGA) and β-lactamase (Bla), which are closely associated with drug-resistant bacterial strains, antibiotic-loaded polymeric vesicles undergo self-immolative structural rearrangement and morphological transitions, leading to sustained release of antibiotics. Enhanced stability, reduced side effects, and bacterial strain-selective drug release were achieved. Considering that Bla is the main cause of bacterial resistance to β-lactam antibiotic drugs, as a further validation, we demonstrate methicillin-resistant S. aureus (MRSA)-triggered release of antibiotics from Bla-degradable polymeric vesicles, in vitro inhibition of MRSA growth, and enhanced wound healing in an in vivo murine model.

Loss-of-function mutations in Angiopoietin-like 3 (Angptl3) are associated with lowered blood lipid levels, making Angptl3 an attractive therapeutic target for the treatment of human lipoprotein metabolism disorders. In this study, we developed a lipid nanoparticle delivery platform carrying Cas9 messenger RNA (mRNA) and guide RNA for CRISPR-Cas9–based genome editing of Angptl3 in vivo. This system mediated specific and efficient Angptl3 gene knockdown in the liver of wild-type C57BL/6 mice, resulting in profound reductions in serum ANGPTL3 protein, low density lipoprotein cholesterol, and triglyceride levels. Our delivery platform is significantly more efficient than the FDA-approved MC-3 LNP, the current gold standard. No evidence of off-target mutagenesis was detected at any of the nine top-predicted sites, and no evidence of toxicity was detected in the liver. Importantly, the therapeutic effect of genome editing was stable for at least 100 d after a single dose administration. This study highlights the potential of LNP-mediated delivery as a specific, effective, and safe platform for Cas9-based therapeutics.

BackgroundDepression is a major mental health issue worldwide, and university students with heavy burdens of study are at a high risk for depression. While a number of studies have been conducted regarding depression among university students in China, there is a lack of information regarding the national prevalence of depression among Chinese university students. Therefore, we performed a meta-analysis to statistically pool the prevalence of depression among Chinese university students.MethodsA systematic search of scientific databases was conducted, including Chinese Web of Knowledge, Embase, PubMed, Wanfang (a Chinese database) and Weipu (a Chinese database) to find relevant publications published between 1995 and December 2015. This was supplemented by a secondary review of the reference lists of all retrieved papers to find additional relevant citations. Studies published in either English or Chinese that provided prevalence estimates of depression in Chinese university students were considered. Prevalence estimates of each eligible study were extracted and pooled in our meta-analysis using a random-effects model.ResultsA total of 39 studies conducted between 1997 and 2015 including 32,694 university students were analyzed. Our results indicate that the overall prevalence of depression among Chinese university students is 23.8% (95% CI: 19.9%–28.5%). Substantial heterogeneity in prevalence estimates was noted. Subgroup analysis revealed that the prevalence of depression among medical students is higher than among other students.ConclusionsOverall, the prevalence of depression among Chinese university students is exceedingly high. This suggests that it is imperative that more attention be given to the development of appropriate mental healthcare strategies for university students in China.

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