Article
Multidisciplinary Sciences
Eliot Y. Zhu, Jacob L. Schillo, Sarina D. Murray, Jesse D. Riordan, Adam J. Dupuy
Summary: Combined BRAF and MEK inhibition is an effective treatment for BRAF-mutant cutaneous melanoma, but drug resistance remains a challenge. This study utilized the Sleeping Beauty transposon system to investigate the mechanisms of drug resistance in melanoma. The findings demonstrated the importance of considering melanoma heterogeneity and identified a potential target for overcoming drug resistance.
Article
Biochemistry & Molecular Biology
Csaba Miskey, Lisa Kesselring, Irma Querques, Gyorgy Abrusan, Orsolya Barabas, Zoltan Ivics
Summary: This study investigates the role of three amino acids in target site selection of the Sleeping Beauty transposase, and demonstrates that altering these amino acids results in increased specificity and enhanced safety of the SB transposon system.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Lucia Lopez-Gil, Amparo Pascual-Ahuir, Markus Proft
Summary: This scientific review highlights the central importance of genomic instability in the aging process and explores the cellular and molecular changes associated with aging, as well as the genetic and epigenetic alterations that contribute to genomic instability.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Natalie Tschorn, Yasemin van Heuvel, Jorn Stitz
Summary: The use of two-component transposon plasmid vector systems can expedite the development of recombinant cell lines, but the undesired stable transfection and sustained expression of the transposase construct can lead to genetic instability. In this study, we established three recombinant cell pools using a Sleeping Beauty-derived vector system and demonstrated stable integration and sustained expression of the transposase for 48 days. To provide an alternative approach, we generated transcripts of the transposase gene in vitro and co-transfected them with donor vector plasmids, resulting in high copy number integrations and expression levels of the gene of interest (GOI). We anticipate that the use of transposase mRNA will contribute to further improvements in cell line development processes.
MOLECULAR BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Sandra Johnen, Nina Harmening, Corinne Marie, Daniel Scherman, Zsuzsanna Izsvak, Zoltan Ivics, Peter Walter, Gabriele Thumann
Summary: As society ages, neurodegenerative diseases are on the rise, making cell-based gene therapy a valuable option for treating diseases like AMD. The stable integration and continuous secretion of PEDF gene in PE cells through SB100X-mediated transfer offers a promising approach for gene addition therapy. Additionally, the random genomic distribution of the PEDF transposon in human PE cells provides valuable insights for further research.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2021)
Review
Virology
Matthias T. Ochmann, Zoltan Ivics
Summary: The Sleeping Beauty transposon system has been widely used as a genetic engineering tool, with extensive studies elucidating the molecular mechanisms and actions during SB transposition process. Structural data on the SB transposase provide a direct insight into the enzyme's functionality, leading to the development of novel SB variants for advanced genetic engineering possibilities. However, many aspects of transposition process remain poorly understood, necessitating further research to explore the structure-function relationships of SB transposition for the development of new vector systems.
Article
Biotechnology & Applied Microbiology
Jaitip Tipanee, Ermira Samara-Kuko, Thierry Gevaert, Marinee K. Chuah, Thierry VandenDriessche
Summary: This study developed a non-viral platform based on Sleeping Beauty transposons and minicircles for genetic modification, allowing efficient expression of CD19-28z.CAR and inactivation of allogeneic TCRs using CRISPR-Cas9. The resulting CAR T cells showed anti-tumor activity against CD19+ tumor cells and induced complete tumor remission in a mouse model, while minimizing TCR alloreactivity and GvHD. This non-viral approach provides an alternative method for generating next-generation CD19-specific CAR T cells, reducing GvHD risk and manufacturing constraints associated with viral vectors.
Article
Oncology
Michiko Kodama, Hiroko Shimura, Jean C. Tien, Justin Y. Newberg, Takahiro Kodama, Zhubo Wei, Roberto Rangel, Kosuke Yoshihara, Airi Kuruma, Aya Nakae, Kae Hashimoto, Kenjiro Sawada, Tadashi Kimura, Nancy A. Jenkins, Neal G. Copeland
Summary: This study identified 19 candidate cancer genes driving uterine leiomyosarcoma (ULMS) through an in vivo Sleeping Beauty transposon mutagenesis screen. ZNF217 and NRDC were highlighted as potential therapeutic targets for ULMS treatment.
Article
Genetics & Heredity
Yiting Zhou, Guangwei Ma, Jiawen Yang, Zenghong Gao, Yabin Guo
Summary: Recent study showed that Sleeping Beauty transposon can integrate into non-TA sites, mainly through aberrant integrations. The consensus sequence of the non-TA target sites corresponds to the transposon end sequence.
FRONTIERS IN GENETICS
(2021)
Article
Biochemical Research Methods
Jong Cheol Jeong, Isaac Hands, Jill M. Kolesar, Mahadev Rao, Bront Davis, York Dobyns, Joseph Hurt-Mueller, Justin Levens, Jenny Gregory, John Williams, Lisa Witt, Eun Mi Kim, Carlee Burton, Amir A. Elbiheary, Mingguang Chang, Eric B. Durbin
Summary: This article focuses on the service models, core services, and a new data harmonization method for Local Data Commons (LDC). It highlights the potential of LDC in identifying and addressing data quality issues, which have traditionally been overlooked. The work aims to raise awareness among LDCs and emphasize their importance to a wider audience.
BMC BIOINFORMATICS
(2022)
Article
Cell Biology
Chenxin Wang, Sen Fang, Yangcan Chen, Na Tang, Guanyi Jiao, Yanping Hu, Jing Li, Qingtong Shan, Xin Wang, Guihai Feng, Qi Zhou, Wei Li
Summary: Due to the difficulties in manipulating DNA repair pathways, high-fidelity targeted integration of large transgenes is inefficient. We developed a robust knock-in strategy called PAINT 3.0, which uses micro-homologues to boost targeted integration in different cells, achieving editing efficiencies up to 80% and minimizing off-target integration. PAINT 3.0 enables high-efficiency genome targeting and functional CAR-T cell production, making it a powerful tool for gene editing and potential for clinical applications.
Article
Biochemistry & Molecular Biology
Yuanyuan Dou, Yan Lin, Tian-yun Wang, Xiao-Yin Wang, Yan-long Jia, Chun-peng Zhao
Summary: The combination of CMV enhancer with CAG promoter showed the highest efficiency for recombinant protein expression in HEK293F cells. Mild hypothermia post-transfection further increased the positive effect of CAG promoter on eGFP expression. CAG promoter outperformed CMV promoter in driving recombinant protein expression.
Article
Multidisciplinary Sciences
Daniel F. Clark, Rachael Schmelz, Nicole Rogers, Nuri E. Smith, Kimberly R. Shorter
Summary: The study found that excess folic acid can impact gene expression, epigenetic marks, and neuromorphology even when MTHFR is functioning normally. Folic acid treatment led to changes in gene expression of epigenetic modifying enzymes, alterations in global DNA methylation and hydroxymethylated DNA. Additionally, folic acid affected dendritic spine densities and histone modifications.
Article
Multidisciplinary Sciences
Nicolas Butel, Agnes Yu, Ivan Le Masson, Filipe Borges, Taline Elmayan, Christelle Taochy, Nial R. Gursanscky, Jiangling Cao, Shengnan Bi, Anne Sawyer, Bernard J. Carroll, Herve Vaucheret
Summary: The research reveals that there are discrepancies in the epigenetic behavior of transgenes and endogenous genes in Arabidopsis, indicating that they are regulated by different mechanisms.
NATURE COMMUNICATIONS
(2021)
Review
Oncology
Silvia Pomella, Sara G. Danielli, Rita Alaggio, Willemijn B. Breunis, Ebrahem Hamed, Joanna Selfe, Marco Wachtel, Zoe S. Walters, Beat W. Schaefer, Rossella Rota, Janet M. Shipley, Simone Hettmer
Summary: Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children and adolescents, characterized by aberrant muscle differentiation. Abnormalities in the regulatory transcription factors (MRFs) involved in skeletal muscle development contribute to tumorigenesis in RMS. Core regulatory circuitries (CRCs) and hierarchically organized subsets of cells play a role in maintaining the disease-driving fusion oncogene and promoting malignancy in RMS. Understanding the genetic and epigenetic framework of abnormal muscle differentiation in RMS provides insights into its mechanisms and potential therapeutic strategies.
Article
Gastroenterology & Hepatology
Yixin Chen, Philip P. Wong, Lucas Sjeklocha, Clifford J. Steer, M. Behnan Sahin
Article
Biochemistry & Molecular Biology
Lucas Sjeklocha, Yixin Chen, Meghan C. Daly, Clifford J. Steer, Betsy T. Kren
JOURNAL OF CELLULAR BIOCHEMISTRY
(2011)
Article
Medicine, Research & Experimental
Betsy T. Kren, Gretchen M. Unger, Lucas Sjeklocha, Alycia A. Trossen, Vicci Korman, Brenda M. Dietheim-Okita, Mark T. Reding, Clifford J. Steer
JOURNAL OF CLINICAL INVESTIGATION
(2009)
Article
Multidisciplinary Sciences
Lucas M. Sjeklocha, Chang-Won Park, Phillip Y-P Wong, Mark J. Roney, John D. Belcher, Dan S. Kaufman, Gregory M. Vercellotti, Robert P. Hebbel, Clifford J. Steer
Article
Multidisciplinary Sciences
Lucas M. Sjeklocha, Phillip Y. -P. Wong, John D. Belcher, Gregory M. Vercellotti, Clifford J. Steer
Article
Multidisciplinary Sciences
Timothy K. Eitas, Wesley Stepp, Lucas Sjeklocha, Clayton Long, Caitlin Riley, James Callahan, Yolanda Sanchez, Peter Gough, Laquanda Knowlin, David van Duin, Shiara Ortiz-Pujols, Samuel Jones, Robert Maile, Zhi Hong, Scott Berger, Bruce Cairns
Correction
Multidisciplinary Sciences
Timothy K. Eitas, Wesley H. Stepp, Lucas Sjeklocha, Clayton V. Long, Caitlin Riley, James Callahan, Yolanda Sanchez, Peter Gough, Laquanda Knowlin, David van Duin, Shiara Ortiz-Pujols, Samuel W. Jones, Robert Maile, Zhi Hong, Scott Berger, Bruce A. Cairns
Review
Medicine, General & Internal
Mark Walsh, Ernest E. Moore, Hunter B. Moore, Scott Thomas, Hau C. Kwaan, Jacob Speybroeck, Mathew Marsee, Connor M. Bunch, John Stillson, Anthony V. Thomas, Annie Grisoli, John Aversa, Daniel Fulkerson, Stefani Vande Lune, Lucas Sjeklocha, Quincy K. Tran
Summary: This review examines the pathophysiology, geographic variation, and historical developments of fixed ratio versus whole blood resuscitation for hemorrhaging trauma patients. It introduces a physiologically driven and goal-directed alternative to guide blood component and factor concentrate administration to severely bleeding trauma patients, with a focus on major studies and upcoming comparative trials.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Emergency Medicine
Lucas Sjeklocha, J. David Gatz
EMERGENCY MEDICINE CLINICS OF NORTH AMERICA
(2021)