Core Viewpoint - The research conducted by Westlake University identifies a significant number of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in the human brain, revealing their genetic control and implications for complex traits, thus providing new insights into the genetic regulatory mechanisms of non-coding RNAs in relation to brain-related complex traits [2][3][12]. Summary by Sections Research Findings - The study analyzed RNA sequencing data from 2,865 human brain cortex samples, identifying 38,441 lncRNAs and 23,548 circRNAs, with 27,453 lncRNAs and all circRNAs not included in the GENCODE database [3][6]. - It determined 15,362 lncRNAs and 1,312 circRNAs with cis-expression quantitative trait loci (eQTL), highlighting the independent nature of eQTLs for lncRNAs and circRNAs compared to their adjacent protein-coding genes [3][7]. - The research found that lncRNA-eQTL and circRNA-eQTL account for an average of 11.14% and 3.20% of the SNP heritability for 14 brain-related complex traits, respectively, compared to 17.19% for protein-coding gene eQTLs [7]. Implications for Complex Traits - The study suggests that certain lncRNAs (e.g., those near VPS45, MAPT, and RGS6) and circRNAs (e.g., those related to GRIN2A) may influence complex traits through non-coding RNA genetic regulation [3][12]. - It integrates lncRNA-eQTL and circRNA-eQTL data with genome-wide association study (GWAS) summary statistics, identifying 795 lncRNAs and 8 circRNAs associated with brain-related traits, indicating shared genetic regulatory mechanisms [7][12]. Research Context - The research addresses the challenge of understanding the molecular mechanisms behind GWAS signals, particularly focusing on non-coding regions where many trait-related variants reside [4][5]. - Previous studies have primarily focused on protein-coding genes, leaving a gap in understanding the genetic control mechanisms of non-coding RNAs, especially in the context of brain-related traits and diseases [6][12].

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].