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

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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.