2-amino-9-[(2R,5R)-3-azido-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-purin-6-one

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 2-amino-9-[(2R,5R)-3-azido-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-purin-6-one
• 化学式: C10H12N8O4
• 分子量: 308.25
• InChiKey: PHGQZPFEHQOLJM-CXIWTZSBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  149
• 氢给体数：
  4
• 氢受体数：
  7

文献信息

• Complexes of RNA and cationic peptides for transfection and for immunostimulation
  申请人：CureVac GmbH

  公开号：EP2484770A1

  公开（公告）日：2012-08-08

  The present invention relates to a complexed RNA, comprising at least one RNA complexed with one or more oligopeptides, wherein the oligopeptide has a length of 8 to 15 amino acids and has the empirical formula (Arg)l;(;Lys)m;(His)n;(Orn)o;(Xaa)x with the majority of the residues being selected from Arg, Lys, His, Orn. The invention further relates to a method for transfecting a cell or an organism, thereby applying the inventive complexed RNA. Additionally, pharmaceutical compositions and kits comprising the inventive complexed RNA, as well as the use of the inventive complexed RNA for transfecting a cell, tissue or an organism and/or for modulating, preferably inducing or enhancing, an immune response are disclosed herein.

  本发明涉及一种复合 RNA，包括至少一种与一种或多种寡肽复合的 RNA，其中寡肽的长度为 8 至 15 个氨基酸，具有经验式 (Arg)l;(;Lys)m;(His)n;(Orn)o;(Xaa)x，大部分残基选自 Arg、Lys、His、Orn。本发明进一步涉及一种转染细胞或生物体的方法，从而应用本发明的复合 RNA。此外，本文还公开了包含本发明络合 RNA 的药物组合物和试剂盒，以及本发明络合 RNA 用于转染细胞、组织或生物体和/或调节、优选诱导或增强免疫反应的用途。
• Composition comprising a complexed (m)RNA and a naked mRNA for providing or enhancing an immunostimulatory response in a mammal and uses thereof
  申请人：CureVac GmbH

  公开号：EP2762165A2

  公开（公告）日：2014-08-06

  The present invention relates to an immunostimulatory composition comprising a) an adjuvant component, comprising or consisting of at least one (m)RNA, complexed with a cationic or polycationic compound, and b) at least one free mRNA, encoding at least one therapeutically active protein, antigen, allergen and/or antibody, wherein the immunostimulatory composition is capable to elicit or enhance an innate and optionally an adaptive immune response in a mammal. The inventive immunostimulatory composition may be a pharmaceutical composition or a vaccine. The invention furthermore relates to a method of preparation of the inventive immunostimulatory composition. The invention also relates to the use of the inventive immunostimulatory composition or its components (for the preparation of a pharmaceutical composition or a vaccine) for the treatment of various diseases. Finally, the invention relates to kits containing the inventive immunostimulatory composition, its components and/or the pharmaceutical composition or vaccine.

  本发明涉及一种免疫刺激组合物，该组合物包含 a) 佐剂成分，该佐剂成分包含或由至少一种（m）RNA 与阳离子或多阳离子化合物复合物组成；以及 b) 至少一种游离 mRNA，该游离 mRNA 编码至少一种具有治疗活性的蛋白质、抗原、过敏原和/或抗体，其中免疫刺激组合物能够诱发或增强哺乳动物的先天性免疫反应，也可选择性地增强适应性免疫反应。本发明的免疫刺激组合物可以是药物组合物或疫苗。本发明还涉及本发明免疫刺激组合物的制备方法。本发明还涉及本发明免疫刺激组合物或其组分（用于制备药物组合物或疫苗）治疗各种疾病的用途。最后，本发明涉及含有本发明免疫刺激组合物、其成分和/或药物组合物或疫苗的试剂盒。
• UTRS INCREASING THE TRANSLATION EFFICIENCY OF RNA MOLECULES
  申请人：ethris GmbH

  公开号：EP3112469A1

  公开（公告）日：2017-01-04

  Described is an RNA molecule comprising (a) a coding region coding for a polypeptide; and (b) upstream of said coding region one or more UTR(s) comprising the sequence as shown in SEQ ID NO:1 or a sequence which shows 1 to 4 substitutions in comparison to SEQ ID NO:1 and which results in an RNA molecule having the same or a higher translation efficiency as an RNA molecule comprising an UTR comprising SEQ ID NO:1; and/or (c) downstream of said coding region one or more UTR(s) comprising the sequence as shown in SEQ ID NO:2 or a sequence which shows 1 to 7 substitutions in comparison to SEQ ID NO:2 and which results in an RNA molecule having the same or a higher translation efficiency as an RNA molecule comprising an UTR comprising SEQ ID NO:2; wherein said polypeptide encoded by said coding region is not a cytochrome b-245 alpha polypeptide (CYBA). Moreover, described is a nucleic acid molecule encoding the RNA molecule according to the present invention. Further, described is a vector comprising the nucleic acid molecule according to the present invention and to a host cell comprising the vector according to the present invention. Further, described is a pharmaceutical composition comprising the RNA molecule according to the present invention and optionally a pharmaceutically acceptable carrier. Moreover, described is a kit comprising the RNA molecule according to the present invention. Finally, described is the use of one or more UTR(s) as defined in (b) and/or one or more UTR(s) as defined in (c) for increasing the efficiency of translating a coding region of an RNA molecule into a polypeptide or a protein encoded by said coding region.

  所述 RNA 分子包括(a)编码多肽的编码区；和(b)所述编码区上游的一个或多个 UTR，该 UTR 包括 SEQ ID NO:1 所示序列或与 SEQ ID NO:1 相比显示 1 至 4 个取代的序列，其产生的 RNA 分子与包括 SEQ ID NO.1 所示 UTR 的 RNA 分子具有相同或更高的翻译效率；和/或(c)所述编码区下游的一个或多个 UTR，该 UTR 包括 SEQ ID NO:2 所示序列或与 SEQ ID NO:1 相比显示 1 至 7 个取代的序列：1；和/或(c) 在所述编码区下游的一个或多个 UTR，其包含 SEQ ID NO:2 中所示的序列或与 SEQ ID NO:2 相比显示 1 至 7 个取代的序列，其导致的 RNA 分子与包含 SEQ ID NO:2 的 UTR 的 RNA 分子具有相同或更高的翻译效率；其中所述编码区编码的所述多肽不是细胞色素 b-245 alpha 多肽（CYBA）。此外，所述的是编码根据本发明的 RNA 分子的核酸分子。此外，还描述了一种包含根据本发明的核酸分子的载体和包含根据本发明的载体的宿主细胞。此外，还描述了一种药物组合物，该组合物包含根据本发明的 RNA 分子和可选的药学上可接受的载体。此外，还描述了一种包含根据本发明的 RNA 分子的试剂盒。最后，描述了(b)中定义的一个或多个 UTR 和/或(c)中定义的一个或多个 UTR 的用途，以提高将 RNA 分子的编码区翻译成由所述编码区编码的多肽或蛋白质的效率。
• COMPOSITION FOR TREATING PROSTATE CANCER (PCA)
  申请人：CureVac AG

  公开号：EP3222290A1

  公开（公告）日：2017-09-27

  The present invention relates to an active (immunostimulatory) composition comprising at least one RNA, preferably an mRNA, encoding at least two (preferably different) antigens capable of eliciting an (adaptive) immune response in a mammal wherein the antigens are selected from the group consisting of PSA (Prostate-Specific Antigen), PSMA (Prostate-Specific Membrane Antigen), PSCA (Prostate Stem Cell Antigen), and STEAP (Six Transmembrane Epithelial Antigen of the Prostate). The invention furthermore relates to a vaccine comprising said active (immunostimulatory) composition, and to the use of said active (immunostimulatory) composition (for the preparation of a vaccine) and/or of the vaccine for eliciting an (adaptive) immune response for the treatment of prostate cancer (PCa), preferably of neoadjuvant and/or hormone-refractory prostate cancers, and diseases or disorders related thereto. Finally, the invention relates to kits, particularly to kits of parts, containing the active (immunostimulatory) composition and/or the vaccine.

  本发明涉及一种活性（免疫刺激）组合物，该活性（免疫刺激）组合物包含至少一种RNA，最好是mRNA，编码至少两种（最好是不同的）能够在哺乳动物体内引起（适应性）免疫应答的抗原，其中抗原选自由PSA（前列腺特异性抗原）、PSMA（前列腺特异性膜抗原）、PSCA（前列腺干细胞抗原）和STEAP（前列腺六种跨膜上皮抗原）组成的组。此外，本发明还涉及一种包含所述活性（免疫刺激）组合物的疫苗，以及所述活性（免疫刺激）组合物（用于制备疫苗）和/或疫苗用于激发（适应性）免疫应答，以治疗前列腺癌（PCa），最好是新辅助治疗和/或激素难治性前列腺癌，以及与之相关的疾病或紊乱。最后，本发明涉及包含活性（免疫刺激）组合物和/或疫苗的试剂盒，特别是部件试剂盒。
• RNA based biomaterial for tissue engineering applications
  申请人：University of Iowa Research Foundation

  公开号：US10335498B2

  公开（公告）日：2019-07-02

  The present disclosure provides compositions and methods useful for tissue engineering including a composition having chemically modified RNA (cmRNA) encapsulated in or complexed with a non-viral delivery vehicle and a biocompatible, bioresorbable scaffold and methods of using the composition to regenerate, for example, bone tissue.

  本公开提供了用于组织工程的组合物和方法，包括一种具有封装在非病毒递送载体中或与非病毒递送载体复合的化学修饰RNA（cmRNA）的组合物和一种生物相容性、生物可吸收支架，以及使用该组合物再生骨组织等的方法。