Article
Medicine, Research & Experimental
Kun Ma, Wenzhe Li, Guang Zhu, Shibo Sun, Hao Chi, Yalin Yin, He Diao, Xiao-Jin Xing, Zhaoming Guo, Li Wang, Weiping Xu, Changhao Cui, Jianqiang Xu
Summary: The CRISPR/Cas9 gene was cloned into a non-viral safe vector Sleeping-Beauty (SB) transposon to construct a safer vector. In addition, PDA/DEX-PEI@HA (PDPH) nanoparticles were developed to facilitate precise CRISPR/Cas9 targeted delivery, showing high transfection efficiency and minimal cytotoxicity. The study highlights the potential of PDA/DEX-PEI25k@HA/pT25pCas9 (PDPH25k/pT(25K)pCas9) as a non-viral gene vector for CRISPR/Cas9 delivery in clinical medication.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Genetics & Heredity
Sarah C. Saunderson, S. M. Ali Hosseini-Rad, Alexander D. McLellan
Summary: Tetracycline-inducible systems are widely used control elements for mammalian gene expression. The G72V mutation in the rtTA-M2 tetracycline activator reduces basal level expression and increases fold-induction. Sensitivity enhancing mutations compensate for the loss of responsiveness caused by the G72V mutation without compromising promoter tightness.
Review
Biochemistry & Molecular Biology
Nicolas Sandoval-Villegas, Wasifa Nurieva, Maximilian Amberger, Zoltan Ivics
Summary: Transposons are mobile genetic elements that have been used as experimental tools to introduce foreign DNA sequences into target cells in a regulated and highly efficient manner. They are supplied as naked nucleic acids or recombinant proteins, making their use simple, safe, and economically competitive. Transposons enable various avenues for genome manipulations in vertebrates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Samantha Baldassarri, Daniela Benati, Federica D'Alessio, Clarissa Patrizi, Eleonora Cattin, Michela Gentile, Angelo Raggioli, Alessandra Recchia
Summary: This study demonstrates the use of SB transposon to engineer HEK293 cells for improved production of chimpanzee Adenovector. By employing genetic engineering and CRISPR/Cas9 technology, the essential genes for chimpanzee Adenoviral DNA replication were successfully integrated into HEK293 cells, leading to significantly enhanced vector production.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Larissa Mattern, Katrin Otten, Csaba Miskey, Matthias Fuest, Zsuzsanna Izsvak, Zoltan Ivics, Peter Walter, Gabriele Thumann, Sandra Johnen
Summary: This study presents a potential treatment option for dry AMD by transferring the BDNF gene into RPE cells. The expression of BDNF in the transfected cells leads to reduced apoptosis rates and stimulated neurite outgrowth.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
Aiping Zhang, Lijian Wang, Josh Haipeng Lei, Zhengqiang Miao, Monica Vishnu Valecha, Peng Hu, Kai Miao, Chu-Xia Deng
Summary: SB Digestor is a new computational algorithm that overcomes biological heterogeneity and accurately detects and defines cancer driver genes, providing more potential candidates for study.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Review
Oncology
Haruna Takeda, Nancy A. Jenkins, Neal G. Copeland
Summary: Cancer genome sequencing studies have identified driver genes for various cancers, but identifying these genes solely from genetic data remains challenging. In vivo forward genetic screens using SB transposon mutagenesis in mice provide a powerful tool for identifying potential cancer driver genes. Comparing driver genes identified in human and mouse tumors can enhance confidence in identifying cancer driver genes.
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
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)
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
Engineering, Biomedical
Lupeng Ye, Stanley Z. Lam, Luojia Yang, Kazushi Suzuki, Yongji Zou, Qianqian Lin, Yueqi Zhang, Paul Clark, Lei Peng, Sidi Chen
Summary: A gene-delivery system called MAJESTIC, which consists of a Sleeping Beauty transposase encoded into an mRNA delivered by an adeno-associated virus, improves the stability and efficiency of transgene integration and expression in immune cells. It allows for the introduction of chimeric antigen receptors (CARs) and other important genes into various immune cell types, enhancing anti-tumor activity.
NATURE BIOMEDICAL ENGINEERING
(2023)
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
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)
Article
Virology
Renuka Rao, Melad Farraha, Grant J. Logan, Sindhu Igoor, Cindy Y. Kok, James J. H. Chong, Ian E. Alexander, Eddy Kizana
Summary: This study compared two production methods for cardiotropic rAAVs, finding that rAAV produced by the traditional HEK293 method outperformed vector produced using the baculovirus/Sf9 system in vitro and in vivo. This underscores the importance of thorough assessment of vector performance when using diverse rAAV production methods.
Article
Pharmacology & Pharmacy
Johanna P. Laakkonen, Johanna Lahteenvuo, Suvi Jauhiainen, Tommi Heikura, Seppo Yla-Herttuala
VASCULAR PHARMACOLOGY
(2019)
Article
Physiology
Suvi Jauhiainen, Johanna P. Laakkonen, Kirsi Ketola, Pyry Toivanen, Tina Nieminen, Takeshi Ninchoji, Anna-Liisa Levonen, Minna U. Kaikkonen, Seppo Yia-Herttuala
FRONTIERS IN PHYSIOLOGY
(2019)
Article
Radiology, Nuclear Medicine & Medical Imaging
Maiju Soikkeli, Mikko I. Kettunen, Riikka Nivajarvi, Venla Olsson, Seppo Ronkko, Johanna P. Laakkonen, Vesa-Pekka Lehto, Jari Kavakka, Sami Heikkinen
CONTRAST MEDIA & MOLECULAR IMAGING
(2019)
Article
Peripheral Vascular Disease
H. H. Pulkkinen, M. Kiema, J. P. Lappalainen, A. Toropainen, M. Beter, A. Tirronen, L. Holappa, H. Niskanen, M. U. Kaikkonen, S. Yla-Herttuala, Johanna P. Laakkonen
Summary: BMP family members regulate VEGFR2 and Notch signaling via TAZ-Hippo pathway in endothelial tip and stalk cell formation. Among them, BMP6 is the first member found to directly regulate both Hippo signaling and neovessel formation, potentially serving as a target in pro/anti-angiogenic therapies.
Article
Hematology
Pierre R. Moreau, Vanesa Tomas Bosch, Maria Bouvy-Liivrand, Kadri Ounap, Tiit Ord, Heidi H. Pulkkinen, Petri Polonen, Merja Heinaniemi, Seppo Yla-Herttuala, Johanna P. Laakkonen, Suvi Linna-Kuosmanen, Minna U. Kaikkonen
Summary: This study aimed to characterize microRNA-related regulatory mechanisms in the aorta during atherosclerosis. The research analyzed miRNA expression changes in different cell types under proatherogenic stimuli and found common miRNA species dominating in all cell types. The study identified potential mechanisms by which miRNAs affect atherogenesis in a cell-type-specific manner.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Annakaisa Tirronen, Nicholas L. Downes, Jenni Huusko, Johanna P. Laakkonen, Tomi Tuomainen, Pasi Tavi, Marja Hedman, Seppo Yla-Herttuala
Summary: Experimental studies have shown that VEGFR-1 signaling plays a crucial role in cardiac remodeling during pressure overload, and its deficiency leads to changes in LVH and increased risk of sudden death.
Article
Clinical Neurology
Sara Keranen, Santeri Suutarinen, Rahul Mallick, Johanna P. Laakkonen, Diana Guo, Ludmila Pawlikowska, Behnam Rezai Jahromi, Tuomas Rauramaa, Seppo Yla-Herttuala, Doug Marchuk, Timo Krings, Timo Koivisto, Michael Lawton, Ivan Radovanovic, Helen Kim, Marie E. Faughnan, Juhana Frosen
Summary: COX2 expression is found in the majority of bAVMs and is associated with inflammation, but not hemorrhage. Further studies are needed to understand the role of COX2 signaling in the pathobiology and clinical course of bAVMs.
ACTA NEUROCHIRURGICA
(2021)
Article
Biochemistry & Molecular Biology
Isidore Mushimiyimana, Henri Niskanen, Mustafa Beter, Johanna P. Laakkonen, Minna U. Kaikkonen, Seppo Yla-Herttuala, Nihay Laham-Karam
Summary: This study identified an endothelial super-enhancer that can significantly increase transgene expression and affect cell division-related pathways by regulating the ADAMTS18 gene, leading to substantial downstream effects on cell proliferation.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Hematology
Suvi Jauhiainen, Miika Kiema, Marja Hedman, Johanna P. Laakkonen
Summary: Smooth muscle cells and endothelial cells undergo phenotypic switching in aortic aneurysms, contributing to degradation of the aortic wall structure. Changes in vascular flow may affect cell remodeling in aortic aneurysms.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Article
Physiology
Miika Kiema, Jaakko K. Sarin, S. Petteri Kauhanen, Jari Torniainen, Hanna Matikka, Emma-Sofia Luoto, Pekka Jaakkola, Petri Saari, Timo Liimatainen, Ritva Vanninen, Seppo Yla-Herttuala, Marja Hedman, Johanna P. Laakkonen
Summary: The study found that wall shear stress (WSS) is associated with media degeneration, elastin content, and aortic wall strength in patients with thoracic aortic aneurysm (TAA). The outer curves of the aortic wall were thinner, more rigid, and tolerated lower failure strains. Higher smooth muscle cell (SMC) density was correlated with lower strength of the aortic wall structure, along with more macrophages detected in patients with severe media degeneration.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Genetics & Heredity
Tiit Ord, Tapio Lonnberg, Valtteri Nurminen, Aarthi Ravindran, Henri Niskanen, Miika Kiema, Kadri Ounap, Maleeha Maria, Pierre R. Moreau, Pashupati P. Mishra, Senthil Palani, Jenni Virta, Heidi Liljenback, Einari Aavik, Anne Roivainen, Seppo Yla-Herttuala, Johanna P. Laakkonen, Terho Lehtimaki, Minna U. Kaikkonen
Summary: Coronary artery disease (CAD) is a global disease with significant genetic factors. By using single-cell and bulk RNA sequencing, this study explores the biological diversity of atherosclerosis-associated cell states and their contribution to CAD risk. The researchers identified disease-associated cell states, with Vcam1 thorn smooth muscle cells showing the highest contribution to CAD heritability. The findings provide insights into CAD risk mechanisms and have implications for precision medicine and tailored therapeutic interventions.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Multidisciplinary Sciences
M. Beter, A. Abdollahzadeh, H. H. Pulkkinen, H. Huang, F. Orsenigo, P. U. Magnusson, S. Yla-Herttuala, J. Tohka, J. P. Laakkonen
Summary: SproutAngio, a Python-based open-source tool, was developed for the automated segmentation and analysis of endothelial lumen space and sprout morphology. It outperforms the widely used ImageJ plugin and provides new methods for endothelial lumen analysis. SproutAngio can contribute to the understanding of blood vessel formation and heterogeneity.
SCIENTIFIC REPORTS
(2023)
Article
Surgery
Jaakko K. Sarin, Miika Kiema, Emma-Sofia Luoto, Annastiina Husso, Marja Hedman, Johanna P. Laakkonen, Jari Torniainen
Summary: Near-infrared spectroscopy (NIRS) can be used to nondestructively evaluate the tissue viability of the human ascending aorta during open-heart surgery, providing decision-making information for surgical repair.
JOURNAL OF SURGICAL RESEARCH
(2023)
Article
Hematology
Oscar Hsin-Fu Liu, Miika Kiema, Mustafa Beter, Seppo Yla-Herttuala, Johanna P. Laakkonen, Minna U. Kaikkonen
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2020)
Meeting Abstract
Physiology
Heidi Pulkkinen, Miika Kiema, Jari Lappalainen, Anu Toropainen, Annakaisa Tirronen, Lari Holappa, Henri Niskanen, Minna Kaikkonen-Maatta, Seppo Yla-Herttuala, Johanna Laakkonen
JOURNAL OF VASCULAR RESEARCH
(2019)