AUMlnc™

In a groundbreaking cardiovascular research study, scientists discovered a novel human-specific long noncoding RNA called INKILN (Inflammatory MKL1-Interacting Long Noncoding RNA) that plays a critical role in vascular smooth muscle cell (VSMC) inflammation. Using AUMlnc™ sdASO™, researchers achieved over 75% knockdown efficiency of INKILN in human coronary artery smooth muscle cells. The study revealed that INKILN is downregulated in contractile VSMCs but significantly activated in human atherosclerosis and abdominal aortic aneurysm. By targeting INKILN with AUMlnc™, scientists demonstrated that this lncRNA functions as a molecular scaffold, physically interacting with both MKL1 (a transcriptional coactivator) and USP10 (a deubiquitinating enzyme). This interaction prevents ubiquitin-dependent degradation of MKL1, thereby promoting proinflammatory gene expression through the NF-κB pathway. The nuclear-targeting capability of AUMlnc™ sdASO™ was particularly crucial for this research, as INKILN primarily functions in the nucleus where it coordinates protein interactions. When AUMlnc™ was administered in a humanized transgenic mouse model of vascular injury, it effectively reduced inflammation and neointimal formation by approximately 65%, highlighting a potential therapeutic approach for vascular diseases. This case study demonstrates how AUMlnc™ can be used to elucidate complex molecular mechanisms of human-specific lncRNAs that would be impossible to achieve through traditional genetic approaches or RNA interference methods with limited nuclear penetration.

Reference: Zhang et al., Circulation, 2023. "INKILN is a Novel Long Noncoding RNA Promoting Vascular Smooth Muscle Inflammation via Scaffolding MKL1 and USP10."

In an innovative cancer pharmacogenomics study, researchers utilized AUMlnc™ sdASO™ to investigate two critical lncRNAs identified as predictors of anti-EGFR therapy response. The study focused on EGFR-AS1 (an antisense lncRNA) and MIR205HG (a host gene lncRNA), which were discovered to predict erlotinib and gefitinib sensitivity independently of established EGFR mutations. Using AUMlnc™, scientists achieved approximately 50-60% knockdown of these lncRNAs in lung cancer cell lines. The research revealed that AUMlnc™-mediated silencing of either EGFR-AS1 or MIR205HG significantly altered the ratio of full-length EGFR (Isoform A) to truncated EGFR (Isoform D), leading to reduced ligand-dependent growth and decreased erlotinib sensitivity. The self-delivering capability of AUMlnc™ sdASO™ was essential for effectively targeting these nuclear-functioning lncRNAs in the hard-to-transfect lung cancer cell lines. Remarkably, in clinical samples, elevated expression of these lncRNAs correlated with improved overall survival in lung adenocarcinoma patients, similar to the trend observed with EGFR-activating mutations. This groundbreaking work demonstrated how AUMlnc™ can help validate lncRNAs as functional biomarkers of drug response, offering potential complementary diagnostic tools for patients who lack established biomarkers but might still benefit from targeted therapies.

Reference: Nath et al., PNAS, 2019. "Discovering long noncoding RNA predictors of anticancer drug sensitivity beyond protein-coding genes."