Modified Mrna(改良的Mrna)研究综述
Modified Mrna 改良的Mrna - However, regulation of m6A‐modified mRNAs by miRNAs in colorectal cancer (CRC), and its effect on progression of CRC, remains to be investigated. [1] However, the significance of m 6 A-modified mRNAs in IMPA has not been elucidated to date. [2] In myeloid leukemia, nuclear reader YTHDC1 bound m6A-modified mRNA, forming nuclear condensates. [3] However, the peculiarities of translation initiation on m6A-modified mRNAs are not fully known. [4] BNT162b2 (PfizerBioNTech) is a nucleoside-modified mRNA that encodes a full-length SARS-CoV-2 Spike (S) protein, a key target of neutralising antibodies, and has demonstrated a 95% reduction of cases in the general population [1]. [5] Here, we used a modified mRNA (modRNA) gene delivery platform to deliver a cocktail of four cardiac-reprogramming genes (Gata4 (G), Mef2c (M), Tbx5 (T) and Hand2 (H)) together with three reprogramming-helper genes (Dominant Negative (DN)-TGFβ, DN-Wnt8a and Acid ceramidase (AC)), termed 7G-modRNA, to induce CM-like cells. [6] Finally, we demonstrate that G residues stabilize the modified mRNA, while the U residues mark maternal RNA for faster degradation in 2-cell mouse embryos. [7] Through immunoprecipitation of all m6A modified mRNAs and sequencing, the researchers identified Myc and Avpr2 as ADPKD relevant targets of Mettl3. [8] gondii and establish CPSF4 as a reader for m6A-modified mRNAs, via a YTH domain within its C-terminus, a feature which is shared with plants. [9] SUMOylation of YTHDF2 has little impact on its ubiquitination and localization, but significantly increases its binding affinity of m6A-modified mRNAs and subsequently results in deregulated gene expressions which accounts for cancer progression. [10] gondii and establish CPSF4 as a reader for m6A-modified mRNAs, via a YTH domain within its C-terminus, a feature which is shared with plants. [11] The nucleoside-modified mRNA after inoculation is transcribed by ribosomes into SARS-CoV2 spike (S) glycoprotein. [12] Furthermore, YTHDF2 globally regulates the turnover of m 6 A-modified mRNAs, including the pro-apoptotic gene BMF. [13] The YTHDF m6A readers are three related proteins with high affinity for m6A-modified mRNA, yet their biological functions remain obscure. [14] Modified mRNA-based gene delivery presents a promising alternative to traditional gene therapy, because modRNA approaches have high potency, non-immunogenicity, greater efficiency and controlled nucleic acid transfer to the body. [15] The reader proteins of m6A, mainly YTH domain-containing proteins, specifically recognize m6A-modified mRNAs and regulate their metabolism. [16] The success of nucleoside-modified mRNAs in lipid nanoparticles (mRNA-LNP) as COVID-19 vaccines heralded a new era of vaccine development. [17] Standard methods, such as Sendai viruses, episomes, and the base-modified mRNA have limitations. [18] For these immunization experiments, lipid nanoparticle-encapsulated, nucleoside-modified mRNA was chosen to express chimeric spikes, since this kind of mRNA vaccine potently activates B cell responses and is comparable with the licensed SARSCoV-2 mRNA vaccines. [19] In a gain‐of‐function study using a TAC mouse model, Pip4k2c is transiently upregulated using a modified mRNA (modRNA) gene delivery platform, which significantly improve heart function, reverse CH and CF, and lead to increased survival. [20] Nucleoside-modified mRNAs formulated in lipid nanoparticles (mRNA-LNP) have proved to be a potent mode of immunization against infectious diseases in preclinical studies, and are being tested for SARS-CoV-2 in humans. [21] These cells, and neonatal fibroblasts, were transdifferentiated into iECs using modified mRNA. [22] Furthermore, we discuss how toxicants can affect the three tiers of regulation directly, and how these effects influence the m6A-modified mRNAs. [23] Modified mRNA (modRNA)-based somatic reprogramming is an effective and safe approach that overcomes the genomic mutation risk caused by viral integrative methods. [24] In cultured cells, both mRNA vectors expressed the corresponding protein, with higher levels observed in the unmodified mRNA, leading to activated macrophages with differential induction of innate immune molecules. [25] Modified mRNA (modRNA) is a promising new gene therapy approach that has safely and effectively delivered genes into different tissues, including the heart. [26] Here, we report that YT521-B homology domain family 1 (YTHDF1), a critical reader protein for N6-methyladenosine-modified mRNA, was significantly downregulated in the prefrontal cortex of young mice after multiple sevoflurane anesthesia exposures. [27] As known m6A readers, insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) are upregulated in most cancers and mediates the enhancement of m6A-modified mRNAs stability. [28] m6A-modified mRNAs were further validated by m6A-immunoprecipition followed by quantitative real-time PCR (m6A-IP-qPCR). [29] We now show that immunization with different doses of unmodified or N(1)-methylpseudouridine-modified mRNA (modified mRNA) in lipid nanoparticles (LNP) encoding the ECTV gene EVM158 induced similarly strong CD8 T cell responses to the epitope TSYKFESV albeit unmodified mRNA-LNP had adverse effects at the inoculation site. [30] To evaluate this hypothesis, we developed a mathematical model that predicts how spatial distribution of VEGF-A produced by delivery of a modified mRNA (AZD8601) accelerates diabetic wound healing. [31] The use of nucleoside-modified mRNA as a pharmacological agent opens immense opportunities for therapeutic, prophylactic, and diagnostic molecular interventions. [32] Clinical trial participants who received a two-dose primary series of the COVID-19 vaccine mRNA-1273 approximately 6 months earlier entered an open-label phase 2a study ( NCT04405076 ) to evaluate the primary objectives of safety and immunogenicity of a single booster dose of mRNA-1273 or variant-modified mRNAs, including multivalent mRNA-1273. [33] Here we describe a rapid efficient serum- and xenogen-free protocol for neutrophil generation, which is based on direct hematoendothelial programming of hiPSCs using ETV2-modified mRNA. [34] Modified mRNA (modRNA) is a safe, non-immunogenic, efficient, transient, local, and controlled nucleic acid delivery system that can overcome the obstacles to DNA-based or viral approaches for cardiac gene delivery. [35] [150 words] Highlights Protein expression from modified mRNAs tends to follow the pattern m1 Ψ > U >mo5U Protein expression correlates with mRNA thermodynamic stability: Ψ≈ m1Ψ > U > mo5U A highly structured CDS correlates with high expression Increased structured mRNAs extend functional half-life. [36] Conclusions: In HeLa cells, for a small set of genes, m 6 A could modulate the translation of modified mRNAs through affecting the splicing patterns. [37] describe a vaccine candidate that is composed of nucleoside-modified mRNA in lipid nanoparticles that encodes the HSV-2 glycoproteins C, D, and E. [38] Transient activation of YAP with a modified mRNA after ischemia-reperfusion stress reduces cardiac inflammation, attenuates cardiac hypertrophic remodeling and helps to salvage the myocardium. [39] Graphical abstract Schematic representation of a method for electrochemical determination of m6A-modified mRNA. [40] These studies reveal that the number and distribution of m6A sites in cellular mRNAs can regulate and influence the composition of the phase-separated transcriptome, and suggest that the cellular properties of m6A-modified mRNAs are governed by liquid–liquid phase separation principles. [41] Specific recognition of these m6A-modified mRNAs by m6A-binding proteins (i. [42] To design the modified mRNA, the 5' cap and poly (A) tail structures were not considered. [43] Here, we show that m6A-modified mRNAs are enriched in SGs, and that m6A-binding YTHDF proteins are critical for SG formation. [44] Herein, through genome-wide profiling of RNA 5-methylcytosine (m5C) modification in zebrafish early embryos, we found that m5C-modified maternal mRNAs display higher stability than non-m5C-modified mRNAs during MZT. [45] Modified mRNAs (mmRNA) has shown a potential to derive safe and high efficient integration-free iPSCs. [46] We identify numerous oncogene RNAs with hypermethylated m5C sites causally linked to their upregulation in UCBs and further demonstrate YBX1 as an m5C ‘reader’ recognizing m5C-modified mRNAs through the indole ring of W65 in its cold-shock domain. [47] by silencing specific genes with RNA interference (RNAi) or increasing expression of specific proteins using modified mRNA), and the design of fusion proteins that modulate lymphocytic function. [48] Synthetic oligonucleotides, such as microRNA mimics and modified mRNAs, have also been gaining more attention as potential RNA delivery tools, given their advantages such as ease of dosage control and low immunogenicity. [49]然而，miRNAs 在结直肠癌 (CRC) 中对 m6A 修饰的 mRNAs 的调节及其对 CRC 进展的影响仍有待研究。 [1] 然而，迄今为止尚未阐明IMPA中m 6 A-修饰的mRNA的重要性。 [2] 在髓性白血病中，核阅读器 YTHDC1 结合 m6A 修饰的 mRNA，形成核凝聚物。 [3] 然而，m6A 修饰的 mRNA 上翻译起始的特性尚不完全清楚。 [4] BNT162b2 (PfizerBioNTech) 是一种核苷修饰的 mRNA，它编码全长 SARS-CoV-2 Spike (S) 蛋白，是中和抗体的关键靶标，已证明在普通人群中病例减少了 95% [1] . [5] 在这里，我们使用修饰的 mRNA (modRNA) 基因传递平台来传递四种心脏重编程基因（Gata4 (G)、Mef2c (M)、Tbx5 (T) 和 Hand2 (H)）以及三个重编程辅助基因的混合物基因（显性阴性 (DN)-TGFβ、DN-Wnt8a 和酸性神经酰胺酶 (AC)），称为 7G-modRNA，用于诱导 CM 样细胞。 [6] 最后，我们证明 G 残基稳定修饰的 mRNA，而 U 残基标记母体 RNA，以便在 2 细胞小鼠胚胎中更快降解。 [7] 通过对所有 m6A 修饰的 mRNA 进行免疫沉淀和测序，研究人员将 Myc 和 Avpr2 确定为 Mettl3 的 ADPKD 相关靶标。 [8] gondii 并建立 CPSF4 作为 m6A 修饰的 mRNAs 的阅读器，通过其 C 端内的 YTH 结构域，与植物共享的特征。 [9] YTHDF2 的 SUMO 化对其泛素化和定位几乎没有影响，但显着增加了其与 m6A 修饰的 mRNA 的结合亲和力，随后导致基因表达失调，从而导致癌症进展。 [10] gondii 并建立 CPSF4 作为 m6A 修饰的 mRNAs 的阅读器，通过其 C 端内的 YTH 结构域，与植物共享的特征。 [11] 接种后核苷修饰的 mRNA 被核糖体转录为 SARS-CoV2 刺突 (S) 糖蛋白。 [12] 此外，YTHDF2 全局性地调节 m 6 A 修饰的 mRNAs 的转换，包括促凋亡基因 BMF。 [13] YTHDF m6A 阅读器是三种相关蛋白，对 m6A 修饰的 mRNA 具有高亲和力，但它们的生物学功能仍不清楚。 [14] 修饰的基于 mRNA 的基因递送是传统基因治疗的一种有前途的替代方案，因为 modRNA 方法具有高效、非免疫原性、更高的效率和可控的核酸转移到身体。 [15] m6A 的阅读蛋白，主要是含 YTH 结构域的蛋白，可特异性识别 m6A 修饰的 mRNA 并调节其代谢。 [16] 作为 COVID-19 疫苗的脂质纳米颗粒 (mRNA-LNP) 中核苷修饰的 mRNA 的成功预示着疫苗开发的新时代。 [17] 标准方法，如仙台病毒、附加体和碱基修饰的 mRNA 具有局限性。 [18]