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Life-span along with Storage space Situations of Universal Glue: A new Materials Assessment.
A single intramuscular injection of BB-301 results in robust inhibition of mutant PABPN1 and concomitant replacement of the codon-optimized PABPN1 protein. The treatment restores muscle strength and muscle weight to wild-type levels as well as improving other physiological hallmarks of the disease in a mouse model of OPMD.Long non-coding RNAs (lncRNAs) are involved in shaping chromosome conformation and regulation of preimplantation development. However, the role of lncRNA during somatic cell nuclear transfer (SCNT) reprogramming remains largely unknown. In the present study, we identified 114 upregulated lncRNAs in the 8-cell SCNT embryos as candidate key molecules involved in nuclear reprogramming in goat. We found that H3K4me3 was an epigenetic barrier in goat nuclear reprogramming that and injection of Kdm5b mRNA greatly improved SCNT embryos development through removal of H3K4me3. We further reported that knockdown of lnc_3712 increased the expression of Kdm5b, which led to H3K4me3 demethylation. Of note, the development of goat SCNT embryos was improved when lnc_3712 was knocked down, whereas the blastocyst rate showed no difference in lnc_3712 and Kdm5b double knockdown SCNT embryos compared with the negative control SCNT embryos. Specifically, in lnc_3712 knockdown SCNT embryos, partial of the transcriptional activity and the expression of critical embryonic genes (Wee1, Ctsb, and Ybx1) were similar with that of in vitro fertilization embryos. Therefore, our results elucidate the critical role of lnc_3712 in regulating the development of goat SCNT embryos via repressing Kdm5b, which advances our current understanding of the role of lncRNAs during nuclear reprogramming.CRISPR effector proteins introduce double-stranded breaks into the mammalian genome, facilitating gene editing by non-homologous end-joining or homology-directed repair. Unlike the more commonly studied Cas9, the CRISPR effector protein Cas12a/Cpf1 recognizes a T-rich protospacer adjacent motif (PAM) and can process its own CRISPR RNA (crRNA) array, simplifying the use of multiple guide RNAs. We observed that the Cas12a ortholog of Lachnospiraceae bacterium MA2020 (Lb2Cas12a) edited mammalian genes with efficiencies comparable to those of AsCas12a and LbCas12a. Compared to these well-characterized Cas12a orthologs, Lb2Cas12a is smaller and recognizes a narrow set of PAM TTTV. We introduced two mutations into Lb2Cas12a, Q571K and C1003Y, that increased its cleavage efficiency for a range of target sequences beyond those of the commonly used Cas12a orthologs AsCas12a and LbCas12a. In addition to the canonical TTTV PAM, this variant, Lb2-KY, also efficiently cleaved target regions with CTTN PAMs. Finally, we demonstrated that Lb2-KY ribonucleoprotein (RNP) complexes edited two hemoglobin target regions useful for correcting common forms of sickle-cell anemia more efficiently than commercial AsCas12a RNP complexes. Thus, Lb2-KY has distinctive properties useful for modifying a range of clinically relevant targets in the human genome.According to the latest global cancer statistics, cancer has become a major threat to human health, but cancer treatment has encountered many bottlenecks. As an emerging topic in epigenetics, N6-methyladenosine (m6A) is the most common internal modification on eukaryotic mRNA, which has attracted increasing attention in recent years. Accumulating studies have shown that aberrant m6A modifications have profound effects on the characteristics of tumors, which undoubtedly led to a significant breakthrough in cancer treatment. Although m6A function as an oncogene or tumor suppressor is not fully revealed, determining its precise function in the development and evolution of malignant tumors is crucial in improving clinical decisions involving targeted therapies. In this review, we briefly introduce the composition of the m6A methylation machinery and mainly summarize the biological mechanism of m6A in cancer cell death, angiogenesis, epithelial-mesenchymal transition (EMT), and therapeutic resistance. Subsequently, we present the exogenous regulatory factors of m6A and highlight the role of m6A on immune cells and cancer immunotherapy. The potential therapeutic strategies of m6A in human cancer are also discussed, considering research gaps and future applications.Cancer is still a major health problem around the world. The treatment failure of cancer has largely been attributed to drug resistance. Competitive endogenous RNAs (ceRNAs) are involved in various biological processes and thus influence the drug sensitivity of cancers. However, a comprehensive characterization of drug-sensitivity-related ceRNAs has not yet been performed. In the present study, we constructed 15 ceRNA networks across 15 anti-cancer drug categories, involving 217 long noncoding RNAs (lncRNAs), 158 microRNAs (miRNAs), and 1,389 protein coding genes (PCGs). We found that these ceRNAs were involved in hallmark processes such as "self-sufficiency in growth signals," "insensitivity to antigrowth signals," and so on. We then identified an intersection ceRNA network (ICN) across the 15 anti-cancer drug categories. We further identified interactions between genes in the ICN and clinically actionable genes (CAGs) by analyzing the co-expressions, protein-protein interactions, and transcription factor-target gene interactions. We found that certain genes in the ICN are correlated with CAGs. Finally, we found that genes in the ICN were aberrantly expressed in tumors, and some were associated with patient survival time and cancer stage.Polyglutamine (polyQ) diseases are inherited neurodegenerative disorders caused by expansion of cytosine-adenine-guanine (CAG)-trinucleotide repeats in causative genes. These diseases include spinal and bulbar muscular atrophy (SBMA), Huntington's disease, dentatorubral-pallidoluysian atrophy, and spinocerebellar ataxias. Targeting expanded CAG repeats is a common therapeutic approach to polyQ diseases, but concomitant silencing of genes with normal CAG repeats may lead to toxicity. Previous studies have shown that CAG repeat-targeting small interfering RNA duplexes (CAG-siRNAs) have the potential to selectively suppress mutant proteins in in vitro cell models of polyQ diseases. see more However, in vivo application of these siRNAs has not yet been investigated. In this study, we demonstrate that an unlocked nucleic acid (UNA)-modified CAG-siRNA shows high selectivity for polyQ-expanded androgen receptor (AR) inhibition in in vitro cell models and that lipid nanoparticle (LNP)-mediated delivery of the CAG-siRNA selectively suppresses mutant AR in the central nervous system of an SBMA mouse model.
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