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

摘要 关于内部合成DNA/RNA的必要性的背景。核酸(DNA/RNA)抗病毒剂 作为一种新兴的治疗学类别，除了基于 小分子和蛋白质生物制品(例如抗体)。FDA批准的一项 越来越多的小干扰RNA(SiRNA)、反义寡核苷酸和针对 SARS-CoV-2，以及目前在临床上测试的一长串核酸治疗药物。独特而适度的 DNA/RNA复杂的化学结构通常需要微调和测试DNA/RNA与各种 二级结构和化学修饰；DNA/RNA的负电荷和亲水性，以及 当给药进入血液时，相关的快速清除血液循环需要进一步的结构 和化学工程，以改善DNA/RNA治疗药物的药代动力学；此外，敏感性 从DNA/RNA到核酸酶的降解和水解需要广泛的化学和结构测试 工程学。为了应对这些挑战，各种结构工程和化学品的迭代测试 经常需要进行修饰，这涉及到合成相应的各种不同的DNA/RNA 二级结构和/或化学修饰。 目前，大多数寡核苷酸DNA/RNA都是可以商业化的。然而，一些独特的修改 DNA/RNA是不可商业化的；此外，DNA/RNA寡核苷酸的内部合成将是 更经济，特别是如果分子和细胞层面的初步检测/筛查的金额较低， 而且肯定比外部供应商(60-聚RNA寡核苷酸需要2-4周)花费的时间更短(&lt；3天)。 在所附报价单中，请查看建议设备的详细信息以及建议设备的报价 MerMade 12DNA/RNA合成仪。

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.