MedComm - Future medicine最新文献

{"title":"Role of next-generation sequencing in revolutionizing healthcare for cancer management","authors":"Om Saswat Sahoo,&nbsp;Hiya Aidasani,&nbsp;Arnab Nayek,&nbsp;Smita Tripathi,&nbsp;Joyeeta Talukdar,&nbsp;Anamta Gul,&nbsp;Deepak Kumar,&nbsp;Ruby Dhar,&nbsp;Subhradip Karmakar","doi":"10.1002/mef2.70001","DOIUrl":"https://doi.org/10.1002/mef2.70001","url":null,"abstract":"<p>Next-generation sequencing (NGS) has emerged as a transformative technology in oncology, revolutionizing cancer diagnostics and personalized treatment strategies. By providing comprehensive insights into the genetic landscape of tumors, NGS enables the identification of critical somatic and germline mutations, copy number variations (CNVs), and gene fusions. Over the past decade, advancements in NGS platforms have led to greater accuracy, speed, and cost-effectiveness, making it an integral part of cancer research and clinical diagnostics. Despite its widespread adoption, significant challenges remain, including the need for improved methods to detect minimal residual disease (MRD) and accurately profile tumor heterogeneity. This review explores the evolution of NGS technologies and their pivotal role in cancer biology, from early diagnostics to therapeutic guidance. It delves into the application of NGS in identifying CNVs and gene fusions, monitoring MRD, and the increasing relevance of targeted NGS and spatial genomics. Furthermore, the integration of spatial transcriptomics is highlighted as a frontier in understanding the tumor microenvironment. By addressing these critical aspects, this review provides a comprehensive overview of how NGS is shaping the future of cancer research and treatment, offering a complete overview of potential NGS applications in scientific and clinical oncology.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined Mendelian randomization and quantitative proteomics analysis to study the influence of thyroid dysfunction on acute ischemic stroke","authors":"Hong-Xia Li,&nbsp;Ying-Ying Han,&nbsp;Hong-Xiang Yu,&nbsp;Lu-Feng Wang,&nbsp;Can Cui,&nbsp;Ling-Ting Jin,&nbsp;Meng-Ru Ge,&nbsp;Xue Gao,&nbsp;Gang Li,&nbsp;Yong-Bo Hu,&nbsp;Bei Zhang","doi":"10.1002/mef2.70002","DOIUrl":"https://doi.org/10.1002/mef2.70002","url":null,"abstract":"<p>Acute ischemic stroke (AIS) is characterized by high morbidity and mortality, making it crucial to identify the risk factors that influence its occurrence and prognosis. Although individuals with thyroid dysfunction exhibit altered stroke patterns, evidence from observational studies remains inconsistent. Herein, we investigated the influence of thyroid dysfunction on stroke progression and prognosis. We combined Mendelian randomization (MR) and tandem mass tag (TMT)-based quantitative proteomics analysis to study the influence of thyroid dysfunction on AIS. Differentially expression proteins (DEPs) were subsequently identified, functional enrichment analysis was performed, and a protein–protein interaction (PPI) network was constructed. Protein alterations were further validated by western blot. MR analysis revealed a causal association between thyroid disorders and ischemic stroke. DEP analysis identified 38 downregulated proteins and five upregulated proteins. Functional enrichment analysis and PPI network construction highlighted the importance of immune response activation and acute phase pathways, along with the suppression of focal adhesion, regulation of the actin cytoskeleton, and platelet activation pathways. Vasodilator-stimulated phosphoprotein, MYL12B, MYL6, and TPM4 were identified as key DEPs significantly associated with pathological pathways and were verified by western blot. The identification of these key proteins and pathways provides new perspectives for investigating the progression and prognosis of AIS.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small but mighty: Platelets as multifunctional architects of tumor metastasis and immune regulation","authors":"Leyi Tang,&nbsp;Hubing Shi,&nbsp;Yong Luo","doi":"10.1002/mef2.70000","DOIUrl":"https://doi.org/10.1002/mef2.70000","url":null,"abstract":"<p>Platelets play an irreplaceable role in hemostasis and wound healing. However, beyond these classical roles, as the smallest anucleate cells in the blood stream, they are crucial for immune response which have inflammatory functions through specialized receptors and different signaling pathways, influencing both innate and adaptive immune response. Furthermore, many research have proved that platelets significantly contribute to tumor metastasis and are associated with poor prognoses in cancer patients through its coagulability and supporting an immunosuppressive tumor microenvironment. When tumor cells detach from the primary tumor mass and enter the bloodstream, they rapidly initiate the direct activation and adhesion of platelets, forming a protective microenvironment. This environment shields circulating tumor cells (CTCs) from the mechanical shear forces of blood flow and immune surveillance. Here we delve into the interaction between platelets and immunomodulation and explore the multifaceted roles and underlying mechanisms by which platelets influence tumor cell metastasis and tumor growth. Furthermore, we also discussed the diagnostic role of platelets in cancer occurrence and progression, as well as the feasibility and prospects of targeting platelets for antitumor immunotherapy. This review provides a multidimensional perspective and reference for platelet-related cancer treatment strategies and diagnosis.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.70000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142641907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking longevity: How blocking IL-11 signaling could extend healthspan and lifespan","authors":"L. S. C. Lok,&nbsp;O. Monteiro,&nbsp;D. T. Baptista-Hon","doi":"10.1002/mef2.101","DOIUrl":"https://doi.org/10.1002/mef2.101","url":null,"abstract":"&lt;p&gt;We highlight a recent study published in &lt;i&gt;Nature&lt;/i&gt; which explored the role of interleukin-11 (IL-11), a pro-inflammatory cytokine, in aging.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The study demonstrates how inhibiting IL-11 signaling can positively impact both healthspan and lifespan in mice, suggesting a novel target for antiaging therapies with significant implications for enhancing human longevity and quality of life.&lt;/p&gt;&lt;p&gt;Aging is an inevitable process characterized by a gradual decline in physiological functions, increasing vulnerability to diseases as well as mortality. Therefore, understanding the molecular mechanisms that drive aging is crucial for developing interventions that can extend not only the lifespan of people, but also the healthspan defined as the period of life spent in good health. This study found that IL-11 expression in mice increases with age in various tissues, including the liver, visceral gonadal white adipose tissue and skeletal muscle. This suggests that changes in IL-11 may drive the decline in physical and metabolic health observed in older animals. To explore the influence of IL-11, the researchers used genetically engineered mice lacking IL-11 or its receptor. These models showed significant health benefits, including improved metabolic health, reduced inflammation and decreased cellular senescence compared to wild-type controls. The absence of IL-11 signaling also protected the mice from age-related muscle decline, metabolic dysfunction and other age-associated diseases. Importantly, the genetic deletion of IL-11 extended the average lifespan by 24.9% (median lifespan increasing from 121 to 151 weeks) in both male and female mice.&lt;/p&gt;&lt;p&gt;In IL-11-deficient mice, some of the changes such as increased muscle strength were observed even in young mice. Therefore, the researchers administered an anti-IL-11 antibody to aged mice (75 weeks old) for 25 weeks. This resulted in significant improvements in metabolic function, such as enhanced glucose tolerance and insulin sensitivity. Additionally, the mice treated with the antibody exhibited better muscle strength and lower levels of aging biomarkers, including pro-inflammatory cytokines, telomere length and tissue fibrosis. Similar to IL-11 knockout, the administration of anti IL-11 antibodies extended the median lifespan by 22.5% in male mice and 25% in female mice. Intriguingly, both IL-11-knockout mice and anti-IL-11-treated mice showed fewer macroscopic tumors compared to wild type mice at autopsy, suggesting IL-11 inhibition may have beneficial effects on cancer, a common cause of morbidity and mortality in old age. The study also evaluated the mechanisms by which IL-11 influences aging. Inhibiting IL-11 signaling reduced the activity of the ERK–AMPK–mTORC1 pathway, leading to reduced cellular senescence and inflammation. Additionally, IL-11 increased the expression of senescence-associated secretory phenotype factors, which exacerbate aging-related conditions.&lt;/p&gt;&lt;p&gt;The ","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced prediction of preoperative mesenteric lymph node metastasis in colorectal cancer using machine learning with CT-based data","authors":"Lanni Zhou,&nbsp;Lizhu Ouyang,&nbsp;Baoliang Guo,&nbsp;Xiyi Huang,&nbsp;Shaomin Yang,&nbsp;Jialing Pan,&nbsp;Liwen Wang,&nbsp;Ming Chen,&nbsp;Fan Xie,&nbsp;Yunjing Li,&nbsp;Yongxing Du,&nbsp;Xinjie Chen,&nbsp;Qiugen Hu,&nbsp;Fusheng Ouyang","doi":"10.1002/mef2.100","DOIUrl":"https://doi.org/10.1002/mef2.100","url":null,"abstract":"<p>The detection of lymph node (LN) involvement is fundamental for staging colorectal cancer (CRC) and aids in clinical decision-making. Traditionally, determining LN status predominantly relies heavily on histological examination of LN specimens, which can occasionally lead to overtreatment. This study aims to develop a clinical prediction model using machine learning algorithms to assess the risk of mesenteric LN metastasis preoperatively, based on computed tomography images and clinicopathological data from CRC patients. Our findings demonstrate that the predictive model based on XGBoost algorithms exhibited the optimal performance, with area under the curve values consistently stable across training (0.836, 95% confidence interval [CI]: 0.750–0.902) and validation (0.831, 95% CI: 0.688–0.927) cohorts. The model was further elucidated using SHapley Additive Explanation values, which ranked predictors in the XGBoost model by their importance, providing insights into the model's decision-making process. Additionally, the force plot visualizes the contribution of each variable to the prediction for individual samples. The as-obtained model may have the potential to aid in clinical treatment planning, optimize the selection of surgical methods, and guide the decision-making process for adjuvant therapy before surgery.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress on application of dental stem cells in alveolar bone and periodontal regeneration","authors":"Zhaoyong Liu,&nbsp;Chengbin Guo,&nbsp;Jing Guo,&nbsp;Shan Huang,&nbsp;Peng Du","doi":"10.1002/mef2.98","DOIUrl":"https://doi.org/10.1002/mef2.98","url":null,"abstract":"<p>Periodontal disease is a prevalent inflammatory condition affecting the tissues and bone surrounding the teeth, posing significant challenges to oral health. Current treatments often fall short due to incomplete removal of bacteria and plaque, irreversible damage to gums and bone, and their cost and time-consuming nature. Stem cell therapy offers a promising alternative that potentially addresses these limitations. This review delves into the biology, mechanisms, and applications of dental stem cells (DSCs) in alveolar bone and periodontal regeneration. We begin with an overview of various stem cell types and their characteristics, highlighting their role in tissue regeneration and the mechanisms involved. Subsequently, we examine preclinical and clinical studies that demonstrate the efficacy and safety of DSC therapy, showcasing their potential in restoring periodontal health. The discussion also extends to the critical challenges and future directions in the field, emphasizing the necessity for standardized protocols and rigorous research to fully integrate DSC-based therapies into routine clinical practice. This review underscores the transformative potential of DSCs in regenerative dentistry, aiming to provide a comprehensive understanding that can propel further advancements and ultimately improve patient outcomes in periodontal therapy.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.98","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142324653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep learning methods for protein structure prediction","authors":"Yiming Qin,&nbsp;Zihan Chen,&nbsp;Ye Peng,&nbsp;Ying Xiao,&nbsp;Tian Zhong,&nbsp;Xi Yu","doi":"10.1002/mef2.96","DOIUrl":"https://doi.org/10.1002/mef2.96","url":null,"abstract":"<p>Protein structure prediction (PSP) has been a prominent topic in bioinformatics and computational biology, aiming to predict protein function and structure from sequence data. The three-dimensional conformation of proteins is pivotal for their intricate biological roles. With the advancement of computational capabilities and the adoption of deep learning (DL) technologies (especially Transformer network architectures), the PSP field has ushered in a brand-new era of “neuralization.” Here, we focus on reviewing the evolution of PSP from traditional to modern deep learning-based approaches and the characteristics of various structural prediction methods. This emphasizes the advantages of deep learning-based hybrid prediction methods over traditional approaches. This study also provides a summary analysis of widely used bioinformatics databases and the latest structure prediction models. It discusses deep learning networks and algorithmic optimization for model training, validation, and evaluation. In addition, a summary discussion of the major advances in deep learning-based protein structure prediction is presented. The update of AlphaFold 3 further extends the boundaries of prediction models, especially in protein-small molecule structure prediction. This marks a key shift toward a holistic approach in biomolecular structure elucidation, aiming at solving almost all sequence-to-structure puzzles in various biological phenomena.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.96","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142316636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAPability-01: Success of anti-PD-1, HDAC inhibitor, and anti-VEGF combination in colorectal cancer","authors":"Yujie Tan,&nbsp;Yunfang Yu","doi":"10.1002/mef2.97","DOIUrl":"https://doi.org/10.1002/mef2.97","url":null,"abstract":"&lt;p&gt;The CAPability-01 trial, led by Feng Wang et al.,&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; was published in &lt;i&gt;Nature Medicine&lt;/i&gt; on March 04, 2024. This study highlighted that a triplet regimen of the programmed cell death protein-1 (PD-1) monoclonal antibody sintilimab with the histone deacetylase inhibitor (HDACi) chidamide with the anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab significantly improved the progression-free survival (PFS) and response in microsatellite stable/proficient mismatch repair (MSS/pMMR) colorectal cancer (CRC).&lt;/p&gt;&lt;p&gt;CAPability-01 trial is a randomized, open-label, multicenter, Phase 2 clinical trial, that evaluated the efficacy of a triplet therapy (sintilimab, chidamide, and bevacizumab) versus a doublet (sintilimab with chidamide) in patients with unresectable, chemotherapy-refractory, locally advanced or metastatic MSS/pMMR CRC. Forty-eight patients were enrolled and randomly assigned in a 1:1 ratio to receive the triplet or doublet treatment.&lt;/p&gt;&lt;p&gt;The study found that the triplet regimen outperformed the doublet regimen in most key endpoints. More than 50% of the patients presented with liver metastases or lung metastases at baseline. Treatment histories were diverse, with almost half of the patients, particularly in the doublet group, receiving third-line or later treatment. The triplet treatment group exhibited a significantly higher PFS rate and improved overall response rate (ORR) and disease control rate (DCR) compared to the doublet group, with 44% achieving partial response and 28% maintaining stable disease. Subgroup analysis revealed that patients with liver metastases benefited more from the triplet treatment, showing significantly notably better outcomes in PFS (7.3 months vs. 1.4 months, &lt;i&gt;p&lt;/i&gt; = 0.001), ORR (50.0% vs. 8.3%), and DCR (71.4% vs. 8.3%) compared with those on the doublet regimen. In this study, the incidence rates of treatment-related side effects (TEAEs) occurred in 60.0% of patients in the triplet group and 30.4% in the doublet therapy. Grade 3 or higher adverse events included thrombocytopenia, reported in 16.0% of patients receiving triplet therapy compared to 8.7% in the doublet group, and neutropenia, which was reported at 28.0% for the triplet therapy and not at all for the doublet. The triplet regimen appeared promising for patients with MSS/pMMR unresectable advanced or metastatic CRC, providing longer progression-free survival and manageable toxicity.&lt;/p&gt;&lt;p&gt;Despite the advancements in chemotherapy and target therapy, the prognosis of most patients with unresectable locally advanced or metastatic CRC remains poor. Several studies are currently evaluating the effectiveness of immune checkpoint inhibitors (ICIs), antiangiogenesis therapy, and HDAC inhibitors in treating microsatellite instability-high/deficient mismatch repair phenotypes (MSI-H/dMMR) CRC (Table 1). ICIs, like PD-1 antibodies and CTLA-4 antibodies, have demonstrated impressive clinical benefit","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.97","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corneal epithelial ingrowth after small incision lenticule extraction surgery: Insights from a case series and mechanistic studies","authors":"Miao Zhang,&nbsp;Ieng Chong,&nbsp;Xiaoniao Chen,&nbsp;Juan Yang,&nbsp;Linling Cheng,&nbsp;Zonghui Yan","doi":"10.1002/mef2.99","DOIUrl":"https://doi.org/10.1002/mef2.99","url":null,"abstract":"<p>Corneal epithelial ingrowth (EI) is a rare but significant complication following Small Incision Lenticule Extraction (SMILE) surgery. During the procedure, the opaque bubble layer (OBL) formation may create microchannels that disrupt Bowman's layer, providing a pathway for epithelial cells to migrate into the corneal stroma. In this study, we investigated the mechanisms behind EI development and proposed preventive strategies. We analyzed four cases of EI post-SMILE surgery, utilizing anterior segment optical coherence tomography (AS-OCT) and corneal tomography for diagnosis. Preventive measures, including careful anesthetic application and precise suction cone positioning, were employed to minimize OBL formation. Here, we show that subflap debris removal surgery led to significant clinical improvement, with no EI recurrence observed. Our findings suggest that the microchannels created by OBL during surgery may play a crucial role in EI development, challenging previous assumptions that EI is primarily due to trauma at the flap edges. This underscores the importance of precise surgical technique and effective postoperative management. Further research, including clinical studies and advanced imaging, is needed to confirm this proposed mechanism and improve outcomes in refractive surgery. The study highlights the necessity for ongoing advancements in surgical protocols and technology to prevent and manage EI effectively.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.99","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142273081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amplification editing: Achieving accurate replication of genome sequences from short fragments to chromosome length","authors":"Jianqiao Shentu,&nbsp;Yitao Zhao,&nbsp;Shiwei Duan","doi":"10.1002/mef2.95","DOIUrl":"https://doi.org/10.1002/mef2.95","url":null,"abstract":"&lt;p&gt;&lt;i&gt;Cell&lt;/i&gt; recently published the breakthrough of amplification editing (AE) technology by Professor Hao Yin's team. This technology enables the amplification of short sequences to chromosome scale, achieving million-base amplification in both embryonic stem cells and primary cells. This opens up new avenues for precision medicine and genetic research.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;In the biomedical field, the precise manipulation of the genome has long been a primary goal for scientists. From the debut of CRISPR-Cas9 to the sophisticated application of Prime Editing, each technological iteration represents a profound understanding and clever use of the laws of nature. However, although considerable progress has been made in gene editing technology, particularly in single-gene editing, challenges persist when addressing complex genomic structural variations. The current tools are mainly employed to modify specific gene sites, like point mutations or small insertions/deletions, but encounter numerous difficulties when dealing with large-scale structural variations such as gene amplification. The main issues encompass insufficient precision targeting ability, low efficiency, off-target effects, limited scope of application, and high technical complexity. Given that gene amplification plays a crucial role in genetic diseases and cancer, the inability to effectively identify and correct these variations will restrict the understanding of related disease mechanisms and impede the development of effective treatment strategies. Therefore, the development of precise and effective genome structural variation editing tools is an important direction for future research and treatment of complex genetic diseases.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Similar to twin prime editing (twinPE),&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; AE relies on a pair of prime editing guide RNAs (pegRNAs). The key difference is that in AE, the protospacer-adjacent motifs (PAMs) of the two pegRNAs are positioned on either side of the target site, whereas in twinPE, the PAM is inside the target site. This design allows for the generation of complementary 3′ protruding sequences on both sides of the target site. These sequences form a stable double-stranded DNA structure through annealing and binding, significantly improving sequence amplification and target site editing efficiency. The double-sided PAM design enhances pegRNA binding to the target site, increasing editing success rates. The complementary sequence increases the density of pegRNA binding sites, further improving accuracy and efficiency. Additionally, AE technology retains the complete pegRNA recognition site, making the editing product more stable, reducing synthesis errors, and facilitating subsequent processing and analysis (Figure 1).&lt;/p&gt;&lt;p&gt;The core innovation of AE technology lies in its ability to efficiently and accurately replicate DNA sequences from 20 bp to 100 Mb, while effectively avoiding nonspecific amplification and off","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.95","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}