Administrative Supplement (Equipment): Nucleic acid modulators and theranostics for ADAR

行政补充（设备）： ADAR 的核酸调节剂和治疗诊断

• 批准号: 10582378
• 负责人: Guizhi Zhu
• 金额: $ 17.52万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-18 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10582378
• 关键词: Address; Administrative Supplement; Antibodies; Antisense Oligonucleotides; Biological Products; Blood; Blood Circulation; COVID-19 vaccine; Charge; Chemical Engineering; Chemical Structure; Chemicals; Clinic; Complex; DNA; DNA Structure; DNA biosynthesis; Drug Kinetics; Economics; Engineering; Equipment; Hydrolysis; Modification; Molecular; Nucleic Acids; Oligonucleotides; Predisposition; Price; Proteins; RNA; RNA chemical synthesis; RNA vaccine; Small Interfering RNA; Structure; Testing; Time; Vendor; base; hydrophilicity; improved; nuclease; screening; small molecule; theranostics

Summary Background on the need for in-house DNA/RNA synthesis. Nucleic acid (DNA/RNA) theranostics hold tremendous potential as an emerging class of theranostics in addition to conventional theranostics based on small molecules and protein biologics (e.g., antibodies). This has been evidenced by the FDA approvals of an increasing number of small interfering RNA (siRNA), antisense oligonucleotides, and the mRNA vaccines for SARS-CoV-2, and a long list of nucleic acid theranostics currently tested in the clinic. The unique and moderately complex chemical structures of DNA/RNA often require fine-tuning and testing of DNA/RNA with various of secondary structures and chemical modifications; the negative charges and hydrophilicity of DNA/RNA, and the associated rapid clearance from the blood circulation when administrated into the blood requires further structural and chemical engineering to improve the pharmacokinetics of DNA/RNA theranostics; further, the susceptibility of DNA/RNA to nuclease degradation and hydrolysis demands extensive testing of chemical and structural engineering. To address these challenges, iterative testings of various structural engineering and chemical modifications are often needed, which involves the synthesis of the corresponding various DNA/RNA with various secondary structures and/or chemical modifications. Most of the oligonucleotide DNA/RNA are commercially available currently. However, some uniquely modified DNA/RNA are not commercially available; moreover, in-house synthesis of DNA/RNA oligonucleotides would be more economic, especially if the amounts are low for initial testing/screening at the molecular and cellular levels, and would certainly take less time (<3 days) than external vendors (2-4 weeks for 60-mer RNA oligonucleotides). In the attached quote, please review the details of the proposed equipment and quoted prices for the proposed MerMade 12 DNA/RNA synthesizer.

总结 需要内部DNA/RNA合成的背景。核酸（DNA/RNA）治疗诊断学 作为一种新兴的治疗诊断学类别，除了传统的治疗诊断学之外， 小分子和蛋白质生物制剂（例如，抗体）。FDA批准的一种 越来越多的小干扰RNA（siRNA），反义寡核苷酸和mRNA疫苗， SARS-CoV-2，以及目前在临床上测试的一长串核酸治疗诊断学。独特而适度的 DNA/RNA的复杂化学结构通常需要用各种方法对DNA/RNA进行微调和测试， 二级结构和化学修饰; DNA/RNA的负电荷和亲水性， 当施用到血液中时，相关的从血液循环中的快速清除需要进一步的结构上的改进， 和化学工程来改善DNA/RNA治疗诊断剂的药代动力学;此外， DNA/RNA的核酸酶降解和水解需要广泛的化学和结构测试， 工程.为了应对这些挑战，各种结构工程和化学品的迭代测试 通常需要进行修饰，这涉及合成相应的各种DNA/RNA， 二级结构和/或化学修饰。 目前，大多数寡核苷酸DNA/RNA是可商购的。然而，一些独特的修改 DNA/RNA不可商购获得;此外，DNA/RNA寡核苷酸的内部合成将是不可能的。 更经济，特别是如果在分子和细胞水平上用于初始测试/筛选的量较低， 并且肯定比外部供应商（对于60-mer RNA寡核苷酸为2-4周）花费更少的时间（<3天）。 在所附的报价中，请审查拟议设备的详细信息和拟议设备的报价。 MerMade 12 DNA/RNA合成仪。