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Development of an mRNA-based therapeutic vaccine mHTV-03E2 for high-risk HPV-related malignancies Mol. Ther. (IF 12.4) Pub Date : 2024-05-06 Jing Wang, Qixin Wang, Ling Ma, Kai Lv, Lu Han, Yunfeng Chen, Rui Zhou, Haokun Zhou, Hua Chen, Yi Wang, Tingting Zhang, Dongrong Yi, Qian Liu, Yongxin Zhang, Xiaoyu Li, Tingting Cheng, Jinming Zhang, Chunjian Huang, Yijie Dong, Weiguo Zhang, Shan Cen
Human papillomavirus (HPV) 16 and 18 infections are related to many human cancers. Despite several preventive vaccines for high-risk (hr) HPVs, there is still an urgent need to develop therapeutic HPV vaccines for targeting pre-existing hrHPV infections and lesions. In this study, we developed a lipid nanoparticle (LNP)-formulated mRNA-based HPV therapeutic vaccine (mHTV)-03E2, simultaneously targeting
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mRNA-based therapeutic strategies for cancer treatment Mol. Ther. (IF 12.4) Pub Date : 2024-05-03 Thilelli Taibi, Sehyun Cheon, Fabiana Perna, Ly P. Vu
In the rapidly evolving landscape of medical research, the emergence of RNA-based therapeutics is paradigm shifting. It is mainly driven by the molecular adaptability and capacity to provide precision in targeting. The coronavirus disease 2019 pandemic crisis underscored the effectiveness of the mRNA therapeutic development platform and brought it to the forefront of RNA-based interventions. These
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Chandipura viral glycoprotein (CNV-G) promotes Gectosome generation and enables delivery of intracellular therapeutics Mol. Ther. (IF 12.4) Pub Date : 2024-05-03 Xiaojuan Zhang, Quanbin Xu, Zeyu Liu, Jayson B. Ball, Brandon Black, Saheli Ganguly, Michael E. Harland, Samuel Blackman, Stephanie Bryant, Kristi Anseth, Linda Watkins, Xuedong Liu
Overexpression of vesicular stomatitis virus G protein (VSV-G) elevates the secretion of EVs known as gectosomes, which contain VSV-G. Such vesicles can be engineered to deliver therapeutic macromolecules. We investigated viral glycoproteins from several viruses for their potential in gectosome production and intracellular cargo delivery. Expression of the viral glycoprotein (viral glycoprotein from
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Circular RNA vaccines against monkeypox virus provide potent protection against vaccinia virus infection in mice Mol. Ther. (IF 12.4) Pub Date : 2024-04-24 Jinge Zhou, Tianxi Ye, Yun Yang, Entao Li, Kaiyue Zhang, Yuping Wang, Shaohong Chen, Jiang Hu, Kai Zhang, Fang Liu, Rui Gong, Xia Chuai, Zefeng Wang, Sandra Chiu
Since the outbreak of monkeypox (mpox) in 2022, widespread concern has been placed on imposing an urgent demand for specific vaccines that offer safer and more effective protection. Using an efficient and scalable circular RNA (circRNA) platform, we constructed four circRNA vaccines that could induce robust neutralizing antibodies as well as T cell responses by expressing different surface proteins
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Controlling CAR-T cell activity and specificity with synthetic SparX adapters Mol. Ther. (IF 12.4) Pub Date : 2024-04-24 Justin P. Edwards, Jeffrey S. Swers, Janine M. Buonato, Liubov Zaritskaya, C. Jenny Mu, Ankit Gupta, Sigal Shachar, David W. LaFleur, Laura K. Richman, David A. Tice, David M. Hilbert
While conventional chimeric antigen-receptor (CAR)-T therapies have shown remarkable clinical activity in some settings, they can induce severe toxicities and are rarely curative. To address these challenges, we developed a controllable cell therapy where synthetic D-domain-containing proteins (soluble protein antigen-receptor X-linker [SparX]) bind one or more tumor antigens and mark those cells for
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Intrathecal gene therapy for neurologic disease in humans Mol. Ther. (IF 12.4) Pub Date : 2024-04-24 Terence R. Flotte
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Sirt6 protects retinal ganglion cells and optic nerve from degeneration during aging and glaucoma Mol. Ther. (IF 12.4) Pub Date : 2024-04-24 Fan Xia, Shuizhen Shi, Erick Palacios, Wei Liu, Seth E. Buscho, Joseph Li, Shixia Huang, Gianmarco Vizzeri, Xiaocheng Charlie Dong, Massoud Motamedi, Wenbo Zhang, Hua Liu
Glaucoma is characterized by the progressive degeneration of retinal ganglion cells (RGCs) and their axons, and its risk increases with aging. Yet comprehensive insights into the complex mechanisms are largely unknown. Here, we found that anti-aging molecule Sirt6 was highly expressed in RGCs. Deleting Sirt6 globally or specifically in RGCs led to progressive RGC loss and optic nerve degeneration during
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Oncolytic adenovirus in treating malignant ascites: A phase II trial and longitudinal single-cell study Mol. Ther. (IF 12.4) Pub Date : 2024-04-24 Yalei Zhang, Ling Qian, Kun Chen, Sijia Gu, Zhiqiang Meng, Jia Wang, Ye Li, Peng Wang
Malignant ascites is a common complication resulting from the peritoneal spread of malignancies, and currently lacks effective treatments. We conducted a phase II trial (NCT04771676) to investigate the efficacy and safety of oncolytic adenovirus H101 and virotherapy-induced immune response in 25 patients with malignant ascites. Oncolytic virotherapy achieved an increased median time to repeat paracentesis
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Antiangiogenic Variant of TSP-1 Targets Tumor Cells in Glioblastomas Mol. Ther. (IF 12.4) Pub Date : 2024-04-18 Sung Hugh Choi, Kaoru Tamura, Rajiv Kumar Khajuria, Deepak Bhere, Irina Nesterenko, Jack Lawler, Khalid Shah
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Three recent breakthroughs in CAR T cells for the treatment of glioblastoma: Is it the light at the end of the tunnel? Mol. Ther. (IF 12.4) Pub Date : 2024-04-17 Pedro R. Lowenstein, Maria Luisa Varela, Maria G. Castro
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Of LAMA3 and LAMB3: A novel gene therapy for epidermolysis bullosa Mol. Ther. (IF 12.4) Pub Date : 2024-04-17 Patrick O’Connell
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Expanding strategies to resolve psoriasis-like inflammation: Non-canonical NF-κB signaling controls IL-23 production in dendritic cells Mol. Ther. (IF 12.4) Pub Date : 2024-04-17 Teresa Neuwirth, Georg Stary
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Bis-2′-F-cGSASMP isomers encapsulated in cytidinyl/cationic lipids act as potent in situ autologous tumor vaccines Mol. Ther. (IF 12.4) Pub Date : 2024-04-17 Jing Yu, Xiaotong Yu, Xudong Sun, Quanxin Wang, Sijie Long, Runan Ren, Zhu Guan, Zhenjun Yang
Cancer immunotherapy has greatly improved the prognosis of tumor-bearing patients. Nevertheless, cancer patients exhibit low response rates to current immunotherapy drugs, such as PD1 and PDL1 antibodies. Cyclic dinucleotide analogs are a promising class of immunotherapeutic agents. In this study, autologous tumor vaccines, composed of bis-2′-F-cGAMP phosphonothioate isomers (FGA-di-pS-2 or FGA-di-pS-4)
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VCAM-targeting lipid platform brings new hope to the treatment of ischemic stroke Mol. Ther. (IF 12.4) Pub Date : 2024-04-16 Xiang Cao, Feifei Li, Hongliang Xin
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DRP1 bridges complement component C5a and podocyte injury in lupus nephritis Mol. Ther. (IF 12.4) Pub Date : 2024-04-16 Jiaxin Lei, Zhenke Wen
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Metachromatic leukodystrophy: A story of hope woven from sorrow Mol. Ther. (IF 12.4) Pub Date : 2024-04-16 Laura Adang
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Defining mesenchymal stem/stromal cell-induced myeloid-derived suppressor cells using single-cell transcriptomics Mol. Ther. (IF 12.4) Pub Date : 2024-04-16 Hyun Ju Lee, Yoo Rim Choi, Jung Hwa Ko, Jin Suk Ryu, Joo Youn Oh
Mesenchymal stem/stromal cells (MSCs) modulate the immune response through interactions with innate immune cells. We previously demonstrated that MSCs alleviate ocular autoimmune inflammation by directing bone marrow cell differentiation from pro-inflammatory CD11bLy6CLy6G cells into immunosuppressive CD11bLy6CLy6G cells. Herein, we analyzed MSC-induced CD11bLy6C cells using single-cell RNA sequencing
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Switch of ELF3 and ATF4 transcriptional axis programs the amino acid insufficiency-linked epithelial-to-mesenchymal transition Mol. Ther. (IF 12.4) Pub Date : 2024-04-16 Jianxiang Lin, Linjun Hou, Xin Zhao, Jingli Zhong, Yilv Lv, Xiaohua Jiang, Bo Ye, Yunbo Qiao
Epithelial-to-mesenchymal transition (EMT) that endows cancer cells with increased invasive and migratory capacity enables cancer dissemination and metastasis. This process is tightly associated with metabolic reprogramming acquired for rewiring cell status and signaling pathways for survival in dietary insufficiency conditions. However, it remains largely unclear how transcription factor (TF)-mediated
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Evolution of the clinical-stage hyperactive TcBuster transposase as a platform for robust non-viral production of adoptive cellular therapies Mol. Ther. (IF 12.4) Pub Date : 2024-04-16 Joseph G. Skeate, Emily J. Pomeroy, Nicholas J. Slipek, Bryan J. Jones, Bryce J. Wick, Jae-Woong Chang, Walker S. Lahr, Erin M. Stelljes, Xiaobai Patrinostro, Blake Barnes, Trevor Zarecki, Joshua B. Krueger, Jacob E. Bridge, Gabrielle M. Robbins, Madeline D. McCormick, John R. Leerar, Kari T. Wenzel, Kathlyn M. Hornberger, Kirsti Walker, Dalton Smedley, David A. Largaespada, Neil Otto, Beau R. Webber
Cellular therapies for the treatment of human diseases, such as chimeric antigen receptor (CAR) T and natural killer (NK) cells have shown remarkable clinical efficacy in treating hematological malignancies; however, current methods mainly utilize viral vectors that are limited by their cargo size capacities, high cost, and long timelines for production of clinical reagent. Delivery of genetic cargo
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mRNA-LNP vaccine-induced CD8+ T cells protect mice from lethal SARS-CoV-2 infection in the absence of specific antibodies Mol. Ther. (IF 12.4) Pub Date : 2024-04-11 Brian Montoya, Carolina R. Melo-Silva, Lingjuan Tang, Samita Kafle, Peter Lidskiy, Csaba Bajusz, Máté Vadovics, Hiromi Muramatsu, Edit Abraham, Zoltan Lipinszki, Debotri Chatterjee, Gabrielle Scher, Juliana Benitez, Molly M.H. Sung, Ying K. Tam, Nicholas J. Catanzaro, Alexandra Schäfer, Raul Andino, Ralph S. Baric, David R. Martinez, Norbert Pardi, Luis J. Sigal
The role of CD8 T cells in SARS-CoV-2 pathogenesis or mRNA-LNP vaccine-induced protection from lethal COVID-19 is unclear. Using mouse-adapted SARS-CoV-2 virus (MA30) in C57BL/6 mice, we show that CD8 T cells are unnecessary for the intrinsic resistance of female or the susceptibility of male mice to lethal SARS-CoV-2 infection. Also, mice immunized with a di-proline prefusion-stabilized full-length
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Transient TCR-based T cell therapy in a patient with advanced treatment-resistant MSI-high colorectal cancer Mol. Ther. (IF 12.4) Pub Date : 2024-04-06 Solrun Melkorka Maggadottir, Svein Dueland, Nadia Mensali, Hanne Hamre, Per Arne Andresen, Marit Renée Myhre, Hedvig V. Juul, Iris Bigalke, Marianne Lundby, Turid Kirsti Hønnåshagen, Stein Sæbøe-Larssen, Dag Josefsen, Trond Hagtvedt, Sébastien Wälchli, Gunnar Kvalheim, Else Marit Inderberg
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Identification of memory mechanism in tissue-resident stem cells via ANGPTL4 beyond immune cells upon viral antigen exposure Mol. Ther. (IF 12.4) Pub Date : 2024-04-06 Eun-kyung Min, Soo-Rim Kim, Choon-Mi Lee, Kun-Hee Na, Chan Hum Park, Byung-Chul Oh, YunJae Jung, In-Sun Hong
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Engineering allorejection-resistant CAR-NKT cells from hematopoietic stem cells for off-the-shelf cancer immunotherapy Mol. Ther. (IF 12.4) Pub Date : 2024-04-06 Yan-Ruide Li, Yang Zhou, Jiaji Yu, Yichen Zhu, Derek Lee, Enbo Zhu, Zhe Li, Yu Jeong Kim, Kuangyi Zhou, Ying Fang, Zibai Lyu, Yuning Chen, Yanxin Tian, Jie Huang, Xinjian Cen, Tiffany Husman, Jae Min Cho, Tzung Hsiai, Jin J. Zhou, Pin Wang, Benjamin R. Puliafito, Sarah M. Larson, Lili Yang
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Decoding and overcoming T cell exhaustion: Epigenetic and transcriptional dynamics in CAR-T cells against solid tumors Mol. Ther. (IF 12.4) Pub Date : 2024-04-06 Taeyoung Ahn, Eun-Ah Bae, Hyungseok Seo
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Fast, accurate ranking of engineered proteins by target-binding propensity using structure modeling Mol. Ther. (IF 12.4) Pub Date : 2024-04-06 Xiaozhe Ding, Xinhong Chen, Erin E. Sullivan, Timothy F. Shay, Viviana Gradinaru
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A p21-ATD mouse model for monitoring and eliminating senescent cells and its application in liver regeneration post injury Mol. Ther. (IF 12.4) Pub Date : 2024-04-06 Miaomiao Chen, Guoxiu Wu, Yanli Lu, Shiwen Sun, Zhao Yu, Xin Pan, Wenjian Chen, Hongyu Xu, Hua Qiu, Weizhi He, Xiuhua Li, Xicheng Wang, Yi Luo, Yuan Du, Jialing Wu, Ke Wei, Wencheng Zhang, Zhongmin Liu, Zhiying He
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TALEN-mediated intron editing of HSPCs enables transgene expression restricted to the myeloid lineage Mol. Ther. (IF 12.4) Pub Date : 2024-04-06 Eduardo Seclen, Jessica C. Jang, Aminah O. Lawal, Sylvain Pulicani, Alex Boyne, Diane Tkach, Alexandre Juillerat, Philippe Duchateau, Julien Valton
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Interaction of SMAC with a survivin-derived peptide alters essential cancer hallmarks: Tumor growth, inflammation, and immunosuppression Mol. Ther. (IF 12.4) Pub Date : 2024-04-05 Manikandan Santhanam, Swaroop Kumar Pandey, Anna Shteinfer-Kuzmine, Avijit Paul, Nur Abusiam, Ran Zalk, Varda Shoshan-Barmatz
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Hit-and-run epigenome editing durably lowers cholesterol in mice Mol. Ther. (IF 12.4) Pub Date : 2024-04-04 Renzhi Han
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Advances and transgressions of nuclear transport checkpoint inhibitors Mol. Ther. (IF 12.4) Pub Date : 2024-04-04 Jacek Hawiger
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Carrier-free mRNA vaccine induces robust immunity against SARS-CoV-2 in mice and non-human primates without systemic reactogenicity Mol. Ther. (IF 12.4) Pub Date : 2024-04-02 Saed Abbasi, Miki Matsui-Masai, Fumihiko Yasui, Akimasa Hayashi, Theofilus A. Tockary, Yuki Mochida, Shiro Akinaga, Michinori Kohara, Kazunori Kataoka, Satoshi Uchida
Carrier-free naked mRNA vaccines may reduce the reactogenicity associated with delivery carriers; however, their effectiveness against infectious diseases has been suboptimal. To boost efficacy, we targeted the skin layer rich in antigen-presenting cells (APCs) and utilized a jet injector. The jet injection efficiently introduced naked mRNA into skin cells, including APCs in mice. Further analyses
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An innate immune response to adeno-associated virus genomes decreases cortical dendritic complexity and disrupts synaptic transmission Mol. Ther. (IF 12.4) Pub Date : 2024-04-01 Christos M. Suriano, Neerav Kumar, Jessica L. Verpeut, Jie Ma, Caroline Jung, Connor E. Dunn, Brigett V. Carvajal, Ai Vy Nguyen, Lisa M. Boulanger
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Transplantation of dorsal root ganglia overexpressing the NaChBac sodium channel improves locomotion after complete SCI Mol. Ther. (IF 12.4) Pub Date : 2024-03-30 Sonia Hingorani, Guillem Paniagua Soriano, Carlos Sánchez Huertas, Eva María Villalba Riquelme, Eric López Mocholi, Beatriz Martínez Rojas, Ana Alastrué Agudo, Sebastián Dupraz, Antonio Vicente Ferrer Montiel, Victoria Moreno Manzano
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CRISPR-Cas9n-mediated ELANE promoter editing for gene therapy of severe congenital neutropenia Mol. Ther. (IF 12.4) Pub Date : 2024-03-30 Masoud Nasri, Malte U. Ritter, Perihan Mir, Benjamin Dannenmann, Masako M. Kaufmann, Patricia Arreba-Tutusaus, Yun Xu, Natalia Borbaran-Bravo, Maksim Klimiankou, Claudia Lengerke, Cornelia Zeidler, Toni Cathomen, Karl Welte, Julia Skokowa
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Targeting the nuclear long noncoding transcript LSP1P5 abrogates extracellular matrix deposition by trans-upregulating CEBPA in keloids Mol. Ther. (IF 12.4) Pub Date : 2024-03-28 Shuchen Gu, Xin Huang, Shenying Luo, Yunhan Liu, Yimin Khoong, Hsin Liang, Liying Tu, Ruoqing Xu, En Yang, Yixuan Zhao, Min Yao, Tao Zan
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RNAi mediated silencing of STAT3/PD-L1 in tumor-associated immune cells induces robust anti-tumor effects in immunotherapy resistant tumors Mol. Ther. (IF 12.4) Pub Date : 2024-03-27 Shanthi Ganesh, Min Ju Kim, Jenny Lee, Xudong Feng, Krisjanis Ule, Amy Mahan, Harini Sivagurunatha Krishnan, Zhe Wang, Maryam Yahyaee Anzahaee, Garima Singhal, Ilia Korboukh, Jennifer A. Lockridge, Laura Sanftner, Rene Rijnbrand, Marc Abrams, Bob D. Brown
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Evaluation of safety and early efficacy of AAV gene therapy in mouse models of vanishing white matter disease Mol. Ther. (IF 12.4) Pub Date : 2024-03-27 Jessica A. Herstine, Pi-Kai Chang, Sergiy Chornyy, Tamara J. Stevenson, Alex C. Sunshine, Ksenia Nokhrina, Jessica Rediger, Julia Wentz, Tatyana A. Vetter, Erika Scholl, Caleb Holaway, Nettie K. Pyne, Anna Bratasz, Stewart Yeoh, Kevin M. Flanigan, Joshua L. Bonkowsky, Allison M. Bradbury
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GSNOR overexpression enhances CAR-T cell stemness and anti-tumor function by enforcing mitochondrial fitness Mol. Ther. (IF 12.4) Pub Date : 2024-03-27 Qing Niu, Haixiao Zhang, Fang Wang, Xing Xu, Yuechen Luo, Baolin He, Mingxia Shi, Erlie Jiang, Xiaoming Feng
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Anti-CD45 PBD-based antibody-drug conjugates are effective targeted conditioning agents for gene therapy and stem cell transplant Mol. Ther. (IF 12.4) Pub Date : 2024-03-27 Jenny Yeung, Aiyin Liao, Matthew Shaw, Soraia Silva, Winston Vetharoy, Diego Leon Rico, Ian Kirby, Francesca Zammarchi, Karin Havenith, Lolke de Haan, Patrick H. van Berkel, Neil Sebire, Olumide K. Ogunbiyi, Claire Booth, H. Bobby Gaspar, Adrian J. Thrasher, Kerry A. Chester, Persis J. Amrolia
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Need for standardization of cytokine profiling in CAR T cell therapy Mol. Ther. (IF 12.4) Pub Date : 2024-03-26 D. Nathan Biery, David P. Turicek, Caroline Diorio, Brett A. Schroeder, Nirali N. Shah
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Restoring T and B cell generation in X-linked severe combined immunodeficiency mice through hematopoietic stem cells adenine base editing Mol. Ther. (IF 12.4) Pub Date : 2024-03-26 Lu Zhang, Kai Li, Zhiwei Liu, Lisha An, Haikun Wei, Shanshan Pang, Zongfu Cao, Xingxu Huang, Xiaohua Jin, Xu Ma
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In vitro and in vivo validation of the antiviral effect of hCypA against SARS-CoV-2 via binding to the RBD of spike protein Mol. Ther. (IF 12.4) Pub Date : 2024-03-25 Woo-Ri Shin, Do-Young Kim, Sang Yong Kim, Gna Ahn, Dae-Young Park, Jiho Min, Ji-Young Ahn, Yang-Hoon Kim
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Otoferlin gene therapy restores hearing in deaf children Mol. Ther. (IF 12.4) Pub Date : 2024-03-23 John V. Brigande
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Immune tolerance induction by hepatic gene transfer: First-in-human evidence Mol. Ther. (IF 12.4) Pub Date : 2024-03-21 Radoslaw Kaczmarek, Benjamin J. Samelson-Jones, Roland W. Herzog
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Chimeric oncolytic adenovirus to break away from neutralizing antibodies Mol. Ther. (IF 12.4) Pub Date : 2024-03-20 Judit Sanchez Gil, Hirotaka Fudaba, Hiroaki Wakimoto
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APOE2 gene therapy reduces amyloid deposition and improves markers of neuroinflammation and neurodegeneration in a mouse model of Alzheimer disease Mol. Ther. (IF 12.4) Pub Date : 2024-03-19 Rosemary J. Jackson, Megan S. Keiser, Jonah C. Meltzer, Dustin P. Fykstra, Steven E. Dierksmeier, Soroush Hajizadeh, Johannes Kreuzer, Robert Morris, Alexandra Melloni, Tsuneo Nakajima, Luis Tecedor, Paul T. Ranum, Ellie Carrell, YongHong Chen, Maryam A. Nishtar, David M. Holtzman, Wilhelm Haas, Beverly L. Davidson, Bradley T. Hyman
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High-multiplex single-cell imaging analysis reveals tumor immune contexture associated with clinical outcomes after CAR T cell therapy Mol. Ther. (IF 12.4) Pub Date : 2024-03-19 Jin Jin, Li Lin, Jiao Meng, Lijun Jiang, Man Zhang, Yuekun Fang, Wanying Liu, Xiangke Xin, Xiaolu Long, Dong Kuang, Xilai Ding, Miao Zheng, Yicheng Zhang, Yi Xiao, Liting Chen
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Large-scale falsification of research papers risks public trust in biomedical sciences Mol. Ther. (IF 12.4) Pub Date : 2024-03-19 Rory Bricker-Anthony, Roland W. Herzog
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FDA approval of the first cellular therapy for a solid (non-hematologic) cancer Mol. Ther. (IF 12.4) Pub Date : 2024-03-19 James N. Kochenderfer
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In a quest for bivalent mRNA vaccine for respiratory viruses: An effective strategy to overcome antigenic competition Mol. Ther. (IF 12.4) Pub Date : 2024-03-19 Gokulnath Mahalingam, Srujan Marepally
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Tiny CRISPR molecular switch tool opens a new world Mol. Ther. (IF 12.4) Pub Date : 2024-03-19 Yeounsun Oh, Seung Hwan Lee
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Rescue of cone and rod photoreceptor function in a CDHR1-model of age-related retinal degeneration Mol. Ther. (IF 12.4) Pub Date : 2024-03-19 Imran H. Yusuf, Thomas Burgoyne, Ahmed Salman, Michelle E. McClements, Robert E. MacLaren, Peter Charbel Issa
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SOCS3 regulates pathological retinal angiogenesis through modulating SPP1 expression in microglia and macrophages Mol. Ther. (IF 12.4) Pub Date : 2024-03-19 Tianxi Wang, Satoshi Kaneko, Emil Kriukov, David Alvarez, Enton Lam, Yidi Wang, Sara La Manna, Daniela Marasco, Angeles Fernandez-Gonzalez, S. Alex Mitsialis, Stella Kourembanas, Andreas Stahl, Mei Chen, Heping Xu, Petr Baranov, Guoshuai Cai, Ulrich H. von Andrian, Ye Sun
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The role of the mitochondrial protein VDAC1 in inflammatory bowel disease: a potential therapeutic target Mol. Ther. (IF 12.4) Pub Date : 2024-03-13 Ankit Verma, Srinivas Pittala, Belal Alhozeel, Anna Shteinfer-Kuzmine, Ehud Ohana, Rajeev Gupta, Jay H. Chung, Varda Shoshan-Barmatz
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Nuclear AGO2 promotes myocardial remodeling by activating ANKRD1 transcription in failing hearts Mol. Ther. (IF 12.4) Pub Date : 2024-03-11 Rong Xie, Shuai Yuan, Guo Hu, Jiabing Zhan, Kunying Jin, Yuyan Tang, Jiahui Fan, Yanru Zhao, Feng Wang, Chen Chen, Dao Wen Wang, Huaping Li
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In vivo base editing of a pathogenic Eif2b5 variant improves vanishing white matter phenotypes in mice Mol. Ther. (IF 12.4) Pub Date : 2024-03-07 Desirée Böck, Ilma M. Revers, Anastasia S.J. Bomhof, Anne E.J. Hillen, Claire Boeijink, Lucas Kissling, Sabina Egli, Miguel A. Moreno-Mateos, Marjo S. van der Knaap, Niek P. van Til, Gerald Schwank
Vanishing white matter (VWM) is a fatal leukodystrophy caused by recessive mutations in subunits of the eukaryotic translation initiation factor 2B. Currently, there are no effective therapies for VWM. Here, we assessed the potential of adenine base editing to correct human pathogenic VWM variants in mouse models. Using adeno-associated viral vectors, we delivered intein-split adenine base editors
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The extracellular cyclophilin A-integrin β2 complex as a therapeutic target of viral pneumonia Mol. Ther. (IF 12.4) Pub Date : 2024-03-07 Xiaoyuan Bai, Wenxian Yang, Yuna Zhao, Tongtong Cao, Runshan Lin, Pengtao Jiao, Heqiao Li, Huizi Li, Jie Min, Xiaoxiao Jia, He Zhang, Wenhui Fan, Xiaojuan Jia, Yuhai Bi, Wenjun Liu, Lei Sun
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ANKRD22 promotes resolution of psoriasiform skin inflammation by antagonizing NIK-mediated IL-23 production Mol. Ther. (IF 12.4) Pub Date : 2024-03-07 Xichun Xia, Leqing Zhu, Miaomiao Xu, Zhiwei Lei, Hai Yu, Guangqiang Li, Xiao Wang, Hongling Jia, Zhinan Yin, Fang Huang, Yunfei Gao
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On- and off-target effects of paired CRISPR-Cas nickase in primary human cells Mol. Ther. (IF 12.4) Pub Date : 2024-03-07 Julia Klermund, Manuel Rhiel, Thomas Kocher, Kay Ole Chmielewski, Johannes Bischof, Geoffroy Andrieux, Melina el Gaz, Stefan Hainzl, Melanie Boerries, Tatjana I. Cornu, Ulrich Koller, Toni Cathomen
Undesired on- and off-target effects of CRISPR-Cas nucleases remain a challenge in genome editing. While the use of Cas9 nickases has been shown to minimize off-target mutagenesis, their use in therapeutic genome editing has been hampered by a lack of efficacy. To overcome this limitation, we and others have developed double-nickase-based strategies to generate staggered DNA double-strand breaks to