Advanced genetics (Hoboken, N.J.)最新文献

RNA–Protein Interactions

This cover art symbolizes RNA-protein interaction methodologies. The boy's fishing line represents RNA bait, while the hooked carp embodies RNA-binding proteins captured via dynamic interplay. In article number 2500011, Wenkai Yi and Jian Yan dissect cutting-edge techniques–from RNA-centric to protein-centric–that decode these molecular dialogues, emphasizing their roles in gene regulation and disease. The metaphor underscores how innovative tools “reel in” elusive targets, bridging mechanistic discovery with therapeutic potential.

Central nervous system (CNS) disorders are driven by complex genetic and epigenetic factors. While gene-based interventions (siRNA, mRNA, CRISPR systems, etc.) hold transformative potential, their clinical application is severely constrained by inefficient delivery, especially across the blood-brain barrier. Nanocarriers have emerged as transformative platforms that overcome these challenges by enabling efficient BBB penetration while ensuring precise biodistribution control and enhanced therapeutic payload protection. This review explores recent advances in nanoplatform-enabled genetic intervention that overcome the delivery challenges through innovative engineering approaches. We discuss the genetic and epigenetic mechanisms underlying major CNS pathologies, the current limitations of free nucleic acid therapeutics, the development of advanced nanoplatforms that achieve blood-brain barrier penetration and targeted delivery. We further also evaluate therapeutic prospects across disease models while addressing translational challenges in stability, targeting specificity, and manufacturing scalability. By integrating fundamental research with preclinical applications, this review provides both a theoretical framework and practical roadmap for developing next-generation nanotherapeutics for CNS genetic medicine.

RNA–protein interactions are fundamental to cellular processes such as gene regulation and RNA metabolism. Over the past decade, significant advancements in methodologies have transformed the ability to study these interactions with unprecedented resolution and specificity. This review systematically compares RNA- and protein-centric approaches, highlighting their strengths, limitations, and optimal applications. RNA-centric methods, including hybridization-based pulldowns, proximity labeling, and CRISPR-assisted techniques, enable the identification of proteins interacting with specific RNAs, even low-abundance or transient partners. Protein-centric strategies, such as immunoprecipitation-based CLIP-seq, and emerging proximity-tagging methods, map RNA interactomes of RNA-binding proteins with nucleotide precision. This study evaluates key innovations like LACE-seq and ARTR-seq, which minimize cell input requirements, and HyPro-MS, which bypasses genetic modifications. Guidelines for method selection are provided, emphasizing experimental goals, RNA abundance, interaction dynamics, and technical constraints. Critical challenges are also discussed, including capturing low-affinity interactions, resolving RNA structural complexities, and integrating multi-omics data. This review underscores the importance of method-tailoring to biological contexts, offering a roadmap for researchers to navigate the evolving landscape of RNA–protein interaction studies. By bridging technical advancements with practical recommendations, this study aims to accelerate discoveries in RNA biology, therapeutic development, and precision medicine.

This study aims to evaluate the role of a specific gene polymorphism, Cytidine/Uridine Monophosphate Kinase 1 (CMPK1) rs1044457, in predicting the response to gemcitabine-based chemotherapy in patients with NSCLC. A total of 98 NSCLC patients are enrolled in the study. Based on their response, patients are classified as either responders or non-responders. Specific primers are designed to amplify the rs1044457 variant and performed genotyping using restriction fragment length polymorphism (RFLP). The rs1044457 variant showed a statistically significant difference in frequency between responder and non-responder patients. The mutant genotype (TT) is more frequent in non-responder patients (18.75%) compared to responder patients (4%), with an odds ratio [OR] of 5.93 (95% confidence interval [CI] = 1.16–30.25, p = 0.032). Additionally, at the allelic level, the mutant allele (T) is more common in non-responder patients (36.46%) compared to responder patients (23%), with a statistically significant odds ratio of 1.92 (95% CI = 1.03–3.58, p = 0.040). The findings of this study suggest that the mutant allele (allele T) of the rs1044457 variant may serve as a risk factor for resistance to gemcitabine-based chemotherapy in patients with NSCLC.

Integration of human genomics and other omics across different ancestries provides novel, affordable, and systematic approach for target identification. We used Mendelian randomization approaches to unravel causal associations between 2,940 circulating proteins and 19 CVD. We found 218 proteins that impacted risk of one or more CVDs through forward MR (106 and 182 using cis-pQTLs only and cis- + trans-pQTLs, respectively), among which 107 were previously reported as associated with CVD or CVD-related traits. There were 102 proteins replicated (FDR < 5%, 53 with cis-pQTLs only and 88 with cis- + trans-pQTLs) using the FinnGen Olink data. BTN3A2 was highlighted as a novel candidate gene for ischemic stroke, suggesting a crosstalk between immune modulation and stroke pathogenesis. Single cell integration prioritized PAM for stable angina pectoris and ventricular arrhythmia and LPL for peripheral artery disease, whose transcriptional expressions were enriched in cardiomyocytes. Forward and reverse MR found largely non-overlapping proteins (only 2 overlapped: LGALS4 and MMP12), suggesting distinct proteomic causes and consequences of CVD. Our study provides human genetics-based evidence of novel candidate genes, a foundational step towards full-scale causal human biology-based drug discovery for CVD.