Based on engineered or bacterial nucleases, the development of genome editing technologies has opened up the possibility of directly targeting and modifying genomic sequences in almost all eukaryotic cells. Genome editing has extended our ability to elucidate the contribution of genetics to disease by promoting the creation of more accurate cellular and animal models of pathological processes and has begun to show extraordinary potential in a variety of fields, ranging from basic research to applied biotechnology and biomedical research. Recent progress in developing programmable nucleases, such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas-associated nucleases, has greatly expedited the progress of gene editing from concept to clinical practice. Here, we review recent advances of the three major genome editing technologies (ZFNs, TALENs, and CRISPR/Cas9) and discuss the applications of their derivative reagents as gene editing tools in various human diseases and potential future therapies, focusing on eukaryotic cells and animal models. Finally, we provide an overview of the clinical trials applying genome editing platforms for disease treatment and some of the challenges in the implementation of this technology.
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Coronavirus disease 2019 (COVID-19) has brought about a great threat to global public health. Recently, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant B.1.1.529 has been reported in South Africa and induced a rapid increase in COVID-19 cases. On November 24, 2021, B.1.1.529 named Omicron was designated as a variant under monitoring (VUM) by World Health Organization (WHO). Two days later, the Omicron variant was classified as a variant of concern (VOC). This variant harbors a high number of mutations, including 15 mutations in the receptor-binding domain (RBD) of spike. The Omicron variant also shares several mutations with the previous VOC Alpha, Beta, and Gamma variants, which immediately raised global concerns about viral transmissibility, pathogenicity, and immune evasion. Here we described the discovery and characteristics of the Omicron variant, compared the mutations of the spike in the five VOCs, and further raised possible strategies to prevent and overcome the prevalence of the Omicron variant.
Epithelial–mesenchymal transition (EMT) is an essential process in normal embryonic development and tissue regeneration. However, aberrant reactivation of EMT is associated with malignant properties of tumor cells during cancer progression and metastasis, including promoted migration and invasiveness, increased tumor stemness, and enhanced resistance to chemotherapy and immunotherapy. EMT is tightly regulated by a complex network which is orchestrated with several intrinsic and extrinsic factors, including multiple transcription factors, post-translational control, epigenetic modifications, and noncoding RNA-mediated regulation. In this review, we described the molecular mechanisms, signaling pathways, and the stages of tumorigenesis involved in the EMT process and discussed the dynamic non-binary process of EMT and its role in tumor metastasis. Finally, we summarized the challenges of chemotherapy and immunotherapy in EMT and proposed strategies for tumor therapy targeting EMT.
Over the past decades, great interest has been given to biomimetic nanoparticles (BNPs) since the rise of targeted drug delivery systems and biomimetic nanotechnology. Biological vectors including cell membranes, extracellular vesicles (EVs), and viruses are considered promising candidates for targeted delivery owing to their biocompatibility and biodegradability. BNPs, the integration of biological vectors and functional agents, are anticipated to load cargos or camouflage synthetic nanoparticles to achieve targeted delivery. Despite their excellent intrinsic properties, natural vectors are deliberately modified to endow multiple functions such as good permeability, improved loading capability, and high specificity. Through structural modification and transformation of the vectors, they are pervasively utilized as more effective vehicles that can deliver contrast agents, chemotherapy drugs, nucleic acids, and genes to target sites for refractory disease therapy. This review summarizes recent advances in targeted delivery vectors based on cell membranes, EVs, and viruses, highlighting the potential applications of BNPs in the fields of biomedical imaging and therapy industry, as well as discussing the possibility of clinical translation and exploitation trend of these BNPs.
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