诊断治疗双突破：环状核酸引领精准医疗新浪潮

Core Viewpoint - Circular oligonucleotides, including circular RNA (circRNA) and circular single-stranded DNA (CssDNA), are emerging as significant research focuses in biomedicine due to their unique closed-loop structure and superior biological stability, driving advancements in precision medicine [2]. Group 1: Circular Oligonucleotides Overview - Circular oligonucleotides (cOligo) are short-chain nucleic acid molecules with a covalently closed structure, providing higher stability and resistance to nuclease degradation compared to linear oligonucleotides [4]. - The closed structure of circular oligonucleotides allows for greater conformational flexibility, enhancing their advantages in molecular recognition and functional design [4]. Group 2: Applications of Circular RNA (circRNA) - CircRNA can be utilized in vaccine development by encoding antigen proteins, which, when delivered via lipid nanoparticles, induce immune responses [8]. - It plays a role in gene expression regulation by synthesizing specific circRNA that can function as miRNA sponges or gene silencers, delivered to target cells via nanoparticles [8]. - CircRNA is also applicable in cell therapy, encoding CAR or TCR proteins, allowing for in situ generation of CAR-T or TCR-T cells, thus improving development efficiency and reducing costs [8]. - Additional applications include the potential for protein translation, enabling the expression of specific proteins such as tumor immune regulatory cytokines and high-strength structural proteins [8]. Group 3: Circular Single-Stranded DNA (CssDNA) - CssDNA is gaining attention as a key player in gene therapy and biomedical research, revitalizing its role in modern applications and becoming a core driver of next-generation precision medicine [10]. - CssDNA aptamers exhibit strong nuclease resistance and thermal stability, with recent studies achieving the selection of aptamers from circular DNA libraries for targeted delivery [11]. - RCA (Rolling Circle Amplification) using CssDNA templates generates long single-stranded products for signal amplification, widely used in gene therapy [13]. - CssDNA-based miRNA sponges are more stable and efficient than RNA sponges, effectively inhibiting oncogenic miRNAs and promoting tumor suppressor gene expression [13]. Group 4: Company Advancements - The company has successfully developed chemical synthesis methods for circRNA and CssDNA, achieving high purity, stability, and precise modifications, thus providing new options for research and industrial applications [15]. - The successful synthesis of 80nt CssDNA has been validated through mass spectrometry and enzyme digestion, confirming the effectiveness of the circularization process [17][19]. - The company offers customized synthesis services for circular RNA and DNA, with varying lengths and timelines, catering to diverse research needs [20].