Human Mature PCSK9 (153-692) Protein
- Known as:
- Human Mature PCSK9 (153-692) Protein
- Catalog number:
- PC9-H5226
- Product Quantity:
- 200ug
- Category:
- -
- Supplier:
- acrobyosystems
- Gene target:
- Human Mature PCSK9 (153-692) Protein
Related genes to: Human Mature PCSK9 (153-692) Protein
- Gene:
- PCSK9 NIH gene
- Name:
- proprotein convertase subtilisin/kexin type 9
- Previous symbol:
- HCHOLA3
- Synonyms:
- NARC-1, FH3
- Chromosome:
- 1p32.3
- Locus Type:
- gene with protein product
- Date approved:
- 2003-05-13
- Date modifiied:
- 2019-04-23
Related products to: Human Mature PCSK9 (153-692) Protein
Related articles to: Human Mature PCSK9 (153-692) Protein
- Despite the clinical success of small interfering RNA (siRNA) therapeutics, limitations including rapid degradation, off-target effects, and high manufacturing costs hinder broader application. Circular siRNAs, particularly dumbbell-shaped variants (db-siRNAs), offer enhanced stability and prolonged activity but lack scalable production methods. Here, we developed a streamlined platform for db-siRNA biosynthesis using a minimized T4 phage thymidylate synthase () group I intron permuted intron-exon (PIE) system. By embedding essential splicing motifs into one terminal loop, we achieved ∼85% cyclization efficiency both and . Using engineered Nissle 1917 (EcN), we established a low-immunogenicity production system, which could yield functional db-siRNAs at 60 mg/L in a fed-batch fermentation with a 3 L bioreactor. db-siRNAs with 23-bp stems demonstrated optimal gene silencing for over 10 days and effectively reduced target expression when formulated with lipid nanoparticles. Our platform enables rapid, cost-effective production of stable, potent db-siRNAs for preclinical development, addressing key manufacturing challenges in RNA interference (RNAi) therapeutics. - Source: PubMed
Publication date: 2026/07/22
Huang ZhiboWang ShaojiaoLiu JinhaoLin YudeXiao ZhiweiChen TienanShi BoGu SijieZhou RujiangYao ZhengjuGuo Xizhi - Abdominal aortic aneurysms (AAA) are characterized by progressive pathological vascular remodeling and a dysregulated immune microenvironment marked by an imbalance between anti-inflammatory regulatory T cells and proinflammatory T helper 17 (Th17) cells within the aortic wall. The molecular mechanisms governing CD4 T-cell differentiation during AAA development remain incompletely defined. MLL1 (mixed lineage leukemia 1), a histone methyltransferase, has recently been shown to modulate T-cell lineage commitment through epigenetic regulation of transcriptional programs in multiple inflammatory diseases. We, therefore, sought to determine whether MLL1 promotes Th17 polarization during AAA development and to identify signaling pathways through which MLL1 regulates CD4 T-cell infiltration and phenotype. - Source: PubMed
Publication date: 2026/08/20
He XiaobingJuriga NicholasCallow BrennanSalih SamaJoshi AmritaBogle RachaelTsoi Lam CObi AndreaGudjonsson Johann EGallagher KatherineDavis Frank M - Despite the promise of DNA base editors for diverse genome editing applications, their utility remains constrained by off-target effects, which are exacerbated by short spacers in miniature systems and the large size of Cas9-derived editors, which impedes adeno-associated virus (AAV) delivery. Here, guided by structural insights into a compact Cas9d nuclease from Deltaproteobacteria, we developed an efficient Cas9d system (Cas9d) through gRNA and protein engineering, and further developed its base editors (9dBEs). Cas9d and 9dBEs enabled efficient and precise genome editing in human cells. Notably, 9dCBE induced premature termination codons in 89% of mouse pups by microinjection, facilitating robust disease modeling. Furthermore, a single AAV delivering 9dCBE achieved efficient Pcsk9 editing and a concomitant reduction in serum LDL-C levels in mice. Collectively, this study establishes a series of compact, potent genome editing tools poised to advance biological and biomedical translational research. - Source: PubMed
Publication date: 2026/08/19
Xiao QingquanTian ZhijinWeng LuqiXu KunHan DingyiWu ZhaoweiLi JunnanLi ShangpuZhang QijingZhao XiaohuiLi GuolingWei YinghuiGu Zhen - Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a role in hepatic cholesterol metabolism via low density lipoprotein receptor degradation. PCSK9 inhibitors have revolutionized lipid-lowering therapy, providing robust reduction of cardiovascular risk. Large-scale randomized controlled trials and long-term extensions (e.g., FOURIER and EBBINGHAUS trials) have shown no significant adverse effects of PCSK9 inhibitors on neuropsychological testing or patient-reported cognitive outcomes, even with prolonged and intensive lowering of low-density lipoproteins. Pre-clinical studies also suggest PCSK9 as a key regulator of neurobiological processes, including synaptic plasticity, amyloid-beta clearance, neuroinflammation, and blood-brain barrier integrity. Human genetic studies revealed complex, sometimes conflicting associations between PCSK9 variants and risk of Alzheimer's disease, Parkinson's disease, vascular dementia, and amyotrophic lateral sclerosis. In this review, we highlight the pathophysiologic mechanisms, emerging experimental therapeutics and clinical implications of PCSK9 inhibition in neurodegenerative disorders. Long-term adequately powered trials with robust neuropsychological, biomarker, and imaging endpoints, as well as mechanistic studies in human-derived models are needed to establish the cardiovascular and neurocognitive implications of PCSK9 inhibition and guide precision medicine strategies for those at elevated risk of neurodegeneration. - Source: PubMed
Publication date: 2026/08/18
Wang Jia Dong JamesTeo Andrea York TiangXiao BinChao YinxiaZhou Zhi DongTan Brendan Jen-WeiChan Ling-LingRosalie ElviraTan Eng-King - Inclisiran lowers LDL-cholesterol (LDL-C) by inhibiting hepatic PCSK9 synthesis. Whether concomitant statin therapy modifies the magnitude of inclisiran-associated LDL-C reduction in routine clinical practice remains uncertain. In this retrospective single-center observational study, 67 patients treated with inclisiran for at least 9 months were analyzed. Patients previously treated with PCSK9 monoclonal antibodies were excluded. LDL-C values were assessed longitudinally and stratified by concomitant statin therapy. Multivariable linear mixed-effects models were used to evaluate inclisiran-associated percentage LDL-C reduction over time. Thirty-seven patients received concomitant statin therapy and 30 patients did not. Median follow-up was 18 months (IQR 12.5-28). Median LDL-C reduction ranged from approximately - 25% to - 40% across follow-up visits. At 9 months, 10 of 59 patients (16.9%) achieved a ≥ 50% LDL-C reduction. In the primary multivariable longitudinal mixed-effects model, concomitant statin use was not significantly associated with percentage LDL-C reduction (β for no statin vs. statin: 33.1% points; 95% CI - 4.6 to 70.7; p = 0.085). Statin intensity was also not significantly associated with LDL-C reduction (β - 0.11 per percentage point of maximum approved dose; 95% CI - 0.60 to 0.37; p = 0.644). In an exploratory responder analysis, concomitant statin therapy was associated with higher odds of achieving ≥ 50% LDL-C reduction at 9 months (OR 7.69; 95% CI 1.28-45.45; p = 0.026). During follow-up, 18 patients (26.9%) discontinued inclisiran, predominantly due to insufficient LDL-C reduction. In routine clinical practice, neither concomitant statin use nor statin intensity was significantly associated with the magnitude of LDL-C reduction observed during inclisiran therapy. However, responder and attrition sensitivity analyses suggested a possible association between concomitant statin therapy and a more pronounced inclisiran-associated LDL-C response. These findings support the clinical use of inclisiran in heterogeneous real-world populations, while highlighting the potential benefit of maintaining concomitant statin therapy whenever tolerated. - Source: PubMed
Publication date: 2026/08/15
Seidel MaximilianSeibert Felix SAnft MoritzStervbo UlrikBabel NinaWesthoff Timm HBertram Sebastian