MedComm – Biomaterials and Applications最新文献

{"title":"Targeting Delivery of Cyanidin-Loaded With Ti3C2 Nanosheets for Alleviating Vascular Calcification in Chronic Kidney Disease","authors":"Li Yin,&nbsp;Xiaoge Zhang,&nbsp;Huanji Zhang,&nbsp;Changming Xie,&nbsp;Zhengzhipeng Zhang,&nbsp;Dong Wang,&nbsp;Yuning Liu,&nbsp;Bing Dong,&nbsp;Leilei Shi,&nbsp;Jie Liu,&nbsp;Hui Huang","doi":"10.1002/mba2.70037","DOIUrl":"https://doi.org/10.1002/mba2.70037","url":null,"abstract":"<p>Vascular calcification is highly associated with cardiovascular morbidity and mortality among patients with chronic kidney disease (CKD). Despite its clinical severity, no effective therapies exist to halt its progression. Sirtuin 6 (SIRT6) has recently emerged as a promising therapeutic target for vascular calcification. Our prior work demonstrated that SIRT6 activation inhibits vascular calcification by attenuating the osteogenic trans differentiation of vascular smooth muscle cells (VSMCs). While the natural compound cyanidin can activate SIRT6, its clinical translation is hampered by poor bioavailability and the absence of targeted delivery systems. To address this, we developed a dual targeting nanoplatform (TROC) based on Ti₃C₂ nanosheets co-assembled with osteocalcin (OCN) and RANKL antibodies for the targeted delivery of cyanidin. Leveraging data from the Framingham Heart Study offspring cohort and in vitro VSMC models, we first established dietary anthocyanins as an independent protective factor against aortic calcification. We then demonstrated that TROC exhibits excellent stability and dose-dependently reduces calcium deposition in VSMCs. Furthermore, in vivo fluorescence and computed tomography (CT) multimodal imaging confirmed the selective accumulation of TROC at calcification sites and its efficacy in alleviating vascular calcification. This novel drug delivery system represents a promising strategy for advancing the clinical treatment of Vascular calcification.</p>","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.70037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145898507","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":"Correction to “VCAM-1-Functionalized Iron Oxide Nanoclusters for Targeted MRI-Based Diagnosis of Atherosclerosis”","authors":"","doi":"10.1002/mba2.70039","DOIUrl":"https://doi.org/10.1002/mba2.70039","url":null,"abstract":"<p>Lina Papadimitriou, Maria Graigkioti, Eirini, Konstantinos Pagonidis, Yannis Papaharilaou, Anthi Ranella, and Alexandros Lappas. <i>MedComm – Biomaterials and Applications</i> 2025; 4:e70030; pages 1–13.</p><p>In the FIRST page, an AUTHOR's name needs attention. Namely:</p><p>The text: “Eirini Koutsouroubi¹” is incorrect. This should have read as: “Eirini D. Koutsouroubi¹”.</p><p>In the FIRST page, under the AFFILIATIONS, the following need correction. Namely:</p><p>First affiliation, the text: “¹Foundation for Research and Technology-Hellas, Institute of Electronic Structure and Laser, Foundation for Research and Technology-Hellas, Heraklion, Crete, Greece” is incorrect. This should have read as: “Institute of Electronic Structure and Laser, Foundation for Research and Technology-Hellas, Heraklion, Crete, Greece”.</p><p>Third affiliation, the text: “³Knossos Diagnosis Medical Centre, Department of Medical Imaging, Knossos Diagnosis Medical Centre, Heraklion, Crete, Greece” is incorrect. This should have read as: “Department of Medical Imaging, Knossos Diagnosis Medical Centre, Heraklion, Crete, Greece”.</p><p>Fourth affiliation, the text: “⁴Foundation for Research and Technology-Hellas, Institute of Applied and Computational Mathematics, Foundation for Research and Technology-Hellas, Heraklion, Crete, Greece” is incorrect. This should have read as: “Institute of Applied and Computational Mathematics, Foundation for Research and Technology-Hellas, Heraklion, Crete, Greece”.</p><p>In the FIRST page, in the ABSTRACT section, the following need correction. Namely:</p><p>Lines 4 and 5 from the top, the text “Dynamic light scattering and transmission electron microscopy TEM confirmed” is incorrect. This should have read as “Dynamic light scattering (DLS) and transmission electron microscopy (TEM) confirmed”</p><p>We apologize for these errors.</p>","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.70039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145904697","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":"Investigations Into the Influence of Ionizable Lipids on the Stability of Lipid Nanoparticle","authors":"Jie Wang,&nbsp;Zhitong Guo,&nbsp;Jun Yang,&nbsp;Haiyin Yang,&nbsp;Shaoping Jiang,&nbsp;Abid Naeem,&nbsp;Bo Hu,&nbsp;Yuhua Weng,&nbsp;Yuanyu Huang","doi":"10.1002/mba2.70036","DOIUrl":"https://doi.org/10.1002/mba2.70036","url":null,"abstract":"<p>Messenger RNA-loaded lipid nanoparticles (mRNA@LNPs) have achieved remarkable success in vaccine development, but their long-term preservation imposes stringent requirements for transportation and storage. To broaden application of this technology, it is essential to develop LNP formulations with enhanced stability. However, the fundamental rules behind LNP stability remains poorly understood. As a key lipid, the impact of the thermostability of ionizable lipids on LNP formulation's stability remains unexplored. In this study, we investigated the thermostability of two ionizable lipids—an in-house-developed lipid (A1-D1-5) and SM-102, the latter used in FDA-approved mRNA therapeutics—and assessed the stability of LNPs composed of these lipids under various storage conditions. Notably, we found that the size and polydispersity index (PDI) measured by dynamic light scattering (DLS) did not accurately reflect the stability of LNPs. While these indicators showed little change after 44 days of storage at 4°C, the mRNA activity sharply declined within just 14 days of preparation. Additionally, A1-D1-5 demonstrated greater thermostability compared to SM-102, leading to a slower decrease in mRNA activity. Importantly, our findings suggest that replacing ester bonds with amide bonds can significantly improve the thermostability of ionizable lipids. Overall, these results provide valuable insights into optimizing and evaluating the stability of mRNA@LNP formulations.</p>","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.70036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846034","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":"Applications of Lysosome-Targeting Receptors (LTRs) in Targeted Protein Degradation","authors":"Lijian Shen,&nbsp;Ziyi Liang,&nbsp;Ying Zhang,&nbsp;Jing Wen,&nbsp;Jie Gao","doi":"10.1002/mba2.70035","DOIUrl":"https://doi.org/10.1002/mba2.70035","url":null,"abstract":"<p>Lysosome-targeting chimeras (LYTACs) represent a novel class of targeted protein degradation (TPD) technologies that utilize lysosome-targeting receptors (LTRs) to degrade extracellular and membrane-bound proteins. Unlike traditional proteasomal degradation pathways, LYTACs direct target proteins to lysosomes for degradation through receptor-mediated endocytosis, offering a promising solution for targeting previously “undruggable” extracellular proteins. To provide an in-depth analysis of the current state of development, existing challenges, and promising future directions of LYTAC technologies, this review first introduces TPD strategies with a focus on LYTAC. It subsequently enumerates 15 LTRs employed in LYTAC systems, with detailed analysis of 9 representative LTRs and their corresponding targeted protein degradation chimera designs. Additionally, two transmembrane E3 ubiquitin ligases functioning as non-classical LTRs are discussed. Finally, the review concludes by summarizing three major challenges currently facing LYTAC technologies, while presenting potential solutions supported by recent research advancements. This comprehensive analysis aims to provide emerging researchers in the LYTAC field with an updated overview of current developments, while offering valuable insights and research perspectives for scientists actively engaged in LYTAC-related investigations.</p>","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145750814","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":"Recent Advances and Evolving Strategies of Photothermal Immunotherapy in Pancreatic Cancer Treatment","authors":"Zan Hu,&nbsp;Jie Meng","doi":"10.1002/mba2.70034","DOIUrl":"https://doi.org/10.1002/mba2.70034","url":null,"abstract":"<p>Pancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDAC), is very lethal with a poor prognosis. The outcome of traditional treatments for PDAC, including surgery, chemotherapy, and radiotherapy, remains unsatisfactory. Recently, immunotherapy, such as mRNA vaccines, immune checkpoint inhibitors, and chimeric antigen receptor T-cells (CAR-T), has shown encouraging advancement at the early stage and provided new opportunities for pancreatic cancer treatment. However, none of the immunotherapies have induced a significant improvement in the clinical prognosis of PDAC till now. Novel pancreatic cancer therapeutic research and development have attracted scientists' keen interest. Photothermal therapy (PTT) is demonstrated to be able to not only directly induce tumor cell death through localized thermal ablation, but also promote antitumor immune response under appropriate conditions, with the release of damage-associated molecular patterns (DAMPs) and tumor-associated antigens (TAAs) from tumor cells, followed by activation of antigen-presenting cells (APCs) and T cell infiltration to kill tumor cells. This review outlines the current treatment strategies and advances of pancreatic cancer, with a focus on the latest evolving research progress based on PTT and immunotherapy. The application prospects and challenges for photothermal immunotherapy in pancreatic cancer treatment are discussed.</p>","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.70034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145686304","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":"Correction to “A New Paradigm for Precision Drug Delivery in Inflammatory Bowel Disease: Effective Transfer, Enhanced Retention, and Pathology-Targeting Treatment via Biomaterials and Engineered Platforms”","authors":"","doi":"10.1002/mba2.70033","DOIUrl":"https://doi.org/10.1002/mba2.70033","url":null,"abstract":"<p>Gan, R., Ni, E., Li, G. and Chen, W. (2025), A New Paradigm for Precision Drug Delivery in Inflammatory Bowel Disease: Effective Transfer, Enhanced Retention, and Pathology-Targeting Treatment via Biomaterials and Engineered Platforms. MedComm – Biomaterials and Applications, 4: e70022.</p><p>In the <b>Conflict of Interest</b>, the text “The authors declare no conflicts of interest.” was incorrect. This should have read: “Wei Chen is the editorial board member of <i>MedComm - Biomaterials and Applications</i>, but was not involved in the journal's review of or decisions related to this Manuscript. The other authors declared no conflict of interest.”</p><p>The editorial office of <i>MedComm – Biomaterials and Applications</i> apologizes for this error.</p>","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145625916","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":"Dual-Targeting Nanovaccine Eradicates Cancer Stem Cells and Bulk Tumors to Prevent Postoperative Recurrence","authors":"Ting Wang,&nbsp;Zhiqing Pang","doi":"10.1002/mba2.70032","DOIUrl":"https://doi.org/10.1002/mba2.70032","url":null,"abstract":"&lt;p&gt;The dual-targeting NICER (nanovesicle system integrating CSC-specific antigen display, epigenetic nano-regulator encapsulation, and dendritic-cell-targeting aptamer) nanovaccine created by Yanlian Yang's team eradicates both cancer stem cells (CSCs) and bulk tumors to prevent postoperative recurrence [&lt;span&gt;1&lt;/span&gt;], addressing a major clinical challenge in solid tumor therapy where conventional treatments fail to eliminate therapy-resistant CSCs [&lt;span&gt;2, 3&lt;/span&gt;]. This breakthrough strategy overcomes limitations of dendritic cell vaccines (hampered by CSC antigen scarcity [&lt;span&gt;4&lt;/span&gt;] and conventional tumor vaccines (neglecting CSC targeting [&lt;span&gt;5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;NICER, which stands for Integrated Nanovaccine for Cancer Eradication and Recurrence Prevention, consists of three complementary components (Figure 1) [&lt;span&gt;1&lt;/span&gt;]. The core carrier consists of antigenically enriched nanovesicles (ANVs) sourced from tumor cells overexpressing ALDH1A1, a universal CSC marker, facilitating the simultaneous display of a CSC-specific antigen (ALDH1A1) and tumor-associated antigens (TAAs) for the concurrent targeting of CSCs and bulk tumor cells. In these ANVs, the team encapsulated an epigenetic nanoregulator (ENR) that delivers small interfering RNA (siRNA) targeting the YTHDF1 protein; by inhibiting YTHDF1-mediated translation of essential lysosomal protease genes in DCs, the ENR reduces antigen degradation within lysosomes and promotes antigen release into the cytosol, thereby enhancing antigen cross-presentation efficiency through the MHC I pathway. Moreover, the surface attachment of a DC-SIGN-specific aptamer leads the NICER vaccine to dendritic cells located in lymph nodes, significantly increasing its accumulation in these essential immunological induction locations.&lt;/p&gt;&lt;p&gt;Experimental validation confirmed that NICER epigenetically reprogramed DC activity, inducing robust antitumor effects across several models. To be more specific, in murine breast cancer (4T1) and melanoma (B16) models, NICER effectively activated antigen-specific CD8⁺ T cells, as demonstrated by significantly increased IFNγ secretion (***&lt;i&gt;p&lt;/i&gt; &lt; 0.0001 compared to the control vaccine). Concurrently, it enabled the promotion of a substantial pool of splenic CD44⁺ memory T cells, as indicated by a significant increase in the frequency of gp70/ALDH1A1 tetramer-positive cells. Furthermore, by employing a tumor model that was enriched with CSCs, NICER was able to significantly decrease the frequency of postoperative residual ALDH1A1⁺ CSCs by roughly 76% (from 3.29% to 0.79%, *&lt;i&gt;p&lt;/i&gt; &lt; 0.0001 in comparison to the control), therefore effectively inhibiting the regrowth of CSC-driven tumors. In the context of surgical lung metastasis, NICER treatment succeeded in achieving a decrease of metastatic nodules by 75% (&lt;i&gt;p&lt;/i&gt; = 0.0013 compared to the control), and it also increased the median survival by roughly twofold. Interestingly, concomitant delivery of a low","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.70032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145625917","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":"Modular Nanosensing Platforms for Tuberculosis and Beyond: Engineering Biomaterials Toward Cross-Pathogen Diagnostic Universality","authors":"Mei Li,&nbsp;Yuxin Luo,&nbsp;Wenqiang Li,&nbsp;Yiqing Wang,&nbsp;Yunze Tai,&nbsp;Zhiping Deng,&nbsp;Yao Luo","doi":"10.1002/mba2.70031","DOIUrl":"https://doi.org/10.1002/mba2.70031","url":null,"abstract":"<p>Tuberculosis (TB) infects one-quarter of the global population and remains a global health crisis, with persistent diagnostic gaps in sensitivity, speed, and accessibility. Nanobiosensors leverage the unique optical, electrical, and magnetic properties of nanomaterials to enhance signal capture and transduction. Meanwhile, functionalized nanointerfaces reduce interference, enabling portable, multiplexed point-of-care testing (POCT). However, existing platforms are predominantly pathogen-specific, leading to fragmented disease management amidst rising co-infections and antimicrobial resistance. This review introduces a paradigm shift toward modular nanosensing platforms designed for cross-pathogen diagnostic universality. We discuss the engineering principles that unify reconfigurable core nanomaterial scaffolds, plug-and-play biorecognition elements, hierarchical signal amplifiers, and universal sample processors. The plug-and-play approach transforms fragmented, pathogen-specific assays into a cohesive diagnostic platform, facilitating equitable deployment in resource-constrained settings. These platforms dynamically adapt to diverse pathogens, from <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) to viruses, fungi, and parasites, enabling ultrasensitive detection in complex matrices. By integrating recognition, transduction, and processing, reconfigurable systems offer rapid, low-cost, field-deployable diagnostics. Modular nanosensors utilize functionalized interfaces to amplify trace biomarker capture, reduce interference, and enable multiplexing, advancing high-sensitivity, low-cost infectious disease diagnostics. It charts a roadmap toward equitable global health against antimicrobial resistance, addressing fragmentation to tackle co-infections and emerging pandemics in resource-limited settings.</p>","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.70031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145521934","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":"VCAM-1-Functionalized Iron Oxide Nanoclusters for Targeted MRI-Based Diagnosis of Atherosclerosis","authors":"Lina Papadimitriou,&nbsp;Maria Graigkioti,&nbsp;Eirini Koutsouroubi,&nbsp;Konstantinos Pagonidis,&nbsp;Yannis Papaharilaou,&nbsp;Anthi Ranella,&nbsp;Alexandros Lappas","doi":"10.1002/mba2.70030","DOIUrl":"https://doi.org/10.1002/mba2.70030","url":null,"abstract":"<p>This study explores the development and characterization of iron oxide nanoclusters (NCs) functionalized with vascular cell adhesion molecule 1 (VCAM-1) for targeted magnetic resonance imaging (MRI) of early atherosclerotic lesions. The NCs were synthesized via a high-temperature polyol method and functionalized using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) chemistry to enable conjugation with VCAM-1 antibodies. Dynamic light scattering and transmission electron microscopy TEM confirmed controlled growth of NCs with a size ranging from 40 nm, in the parent to 110 nm post-functionalization, maintaining though colloidal stability in aqueous media. Cytotoxicity assays using mesenchymal stem cells (MSCs) demonstrated high biocompatibility. Confocal and electron microscopy confirmed specific binding of VCAM-1-NCs to VCAM-1-overexpressing MSCs under inflammatory conditions, with internalization through the endolysosomal pathway. The functionalized NCs remained bound under shear stress in an orbital flow model, mimicking early atherosclerotic conditions. MRI phantom analysis demonstrated preserved contrast capability despite increased <i>T</i>₂* relaxation times following antibody conjugation. These findings highlight the potential of VCAM-1-NCs as noninvasive imaging agents for early-stage atherosclerosis and vascular inflammation. Although this study is limited by the lack of in vivo validation and therapeutic evaluation, it provides a strong foundation for future translational research.</p>","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.70030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145469518","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":"Magic Permutation: QBEmax Achieves High-Purity C-to-T Base Editing By Combining Cas9 Circular Permutation With Deaminase Domain Inlaying","authors":"Min Li,&nbsp;Shaohua Yao","doi":"10.1002/mba2.70029","DOIUrl":"https://doi.org/10.1002/mba2.70029","url":null,"abstract":"&lt;p&gt;In a recent Nature Biotechnology paper [&lt;span&gt;1&lt;/span&gt;], Kevin Zhao's lab reported a precise cytosine base editor (CBE), QBEmax, which features high product purity, low indel rates, and minimal off-target effects. The design of QBEmax combined both Cas9 circularly permutation and cytosine deaminase domain inlaying, which may restrict the deaminase's flexibility and shields the Cas9-induced R-loop. This configuration might protect the base editing intermediate from endogenous UNG-mediated excision before Cas9 dissociates from the target DNA. As a result, QBEmax achieves higher-purity C-to-T conversions, reduces indel formation, and addresses the long-standing issue of product impurity associated with CBE.&lt;/p&gt;&lt;p&gt;CBEs are a group of gene-editing tools first developed by David Liu's lab in 2016. A typical CBE consists of a cytosine deaminase, Cas9 nickase protein (spCas9-D10A nickase), and one or more copies of uracil DNA glycosylase inhibitor (UGI) [&lt;span&gt;2&lt;/span&gt;]. Guided by a single-guide RNA (sgRNA), the CBE specifically recognizes its complementary DNA sequence to form a RNA/DNA/protein ternary complex. The binding of sgRNA spacer to the target strand of target DNA leads to the dissociation of non-target strand to form an R-loop structure, exposing a stretch of single-stranded DNA (ssDNA) outside the ternary complex. The deaminase preferring ssDNA substrates then converts target cytosines (Cs) into uracils (Us), which are then turned into thymines (Ts) via DNA repair or replication mechanisms, ultimately resulting in a C-to-T base substitution. The introduction of ssDNA break in the target strand by Cas9 nickase will enhance the editing outcome according to sequence of the edited non-target strand, since DNA break usually has a higher priority during DNA repair as compared to non-strand break lesions. Through the concerted action of each element of the editor and the endogenous DNA repair or replication machines, this system enables precise editing of individual bases in the genome without causing DNA double-strand breaks or requiring a donor template, thereby significantly enhancing both the flexibility and accuracy of genome editing. However, despite its advantages, CBEs often lead to insertions/deletions (indels) and undesired editing byproducts such as C-to-G or C-to-A conversions. These side effects mainly arise because the deaminated product U can be recognized and excised by endogenous uracil-DNA glycosylase (UNG), generating an apurinic/apyrimidinic (AP or abasic) sites. In many cases, the AP sites are recognized by the AP endonuclease, mainly APE1, which cleaves the DNA backbone at the 5’ side of the AP site to produce a single DNA strand break. This break, together with the nick of the target strand, might be considered as double strand breaks and fixed through error prone DNA repair pathways, such non-homologous end joining (NHEJ) pathway. In other cases, the AP sites will be fixed via DNA translesion synthesis involved mechanisms,","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.70029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145406594","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}