Review
Microbiology
Maria Bousali, George Papatheodoridis, Dimitrios Paraskevis, Timokratis Karamitros
Summary: HBV is an Old World virus with a high mutation rate, originating in Africa alongside Homo sapiens. It can lead to chronic infection by integrating its genome into host DNA, affecting various genes including those related to cell proliferation and oncogenes.
Article
Oncology
Zhimin Chen, Weijie Hao, Jingzhi Tang, Wei-Qiang Gao, Huiming Xu
Summary: CSTF2 is highly expressed in HCC and is correlated with a poor prognosis and high histological grade. The knockout of CSTF2 inhibits the tumorigenesis and progression of HCC. Moreover, CSTF2 is associated with enhanced glycolysis.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Teng-Cheong Ha, Maike Stahlhut, Michael Rothe, Gabi Paul, Violetta Dziadek, Michael Morgan, Martijn Brugman, Boris Fehse, Olga Kustikova, Axel Schambach, Christopher Baum
Summary: Retroviral insertional mutagenesis is a risk in gene therapy and can be used to identify genes that enhance hematopoietic stem cell competitiveness. Studies have shown that a single insertion event may dysregulate distal and multiple genes. Furthermore, multiple genes within a common insertion site can have both positive and negative impacts on hematopoiesis.
HUMAN GENE THERAPY
(2021)
Article
Multidisciplinary Sciences
Kristen F. Rueb, David L. Stachura
Summary: The differentiation of hematopoietic stem and progenitor cells in vertebrate animals and the importance of studying this process using zebrafish as a model organism were discussed. Current methods for assessing blood cell numbers and their limitations were addressed, with a call for developing more cost-effective and efficient approaches for quantitating blood cells.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2021)
Article
Multidisciplinary Sciences
Hao Zhang, Bo Li
Summary: NIMA-related kinase 6 (NEK6) is over-expressed in hepatocellular carcinoma (HCC) and is correlated with clinical features such as hepatitis B virus infection and tumor diameter. Down-regulating NEK6 expression inhibits the migration and invasion capabilities of HCC cells and suppresses tumor growth.
Review
Pharmacology & Pharmacy
Maria Lina Tornesello, Anna Lucia Tornesello, Noemy Starita, Andrea Cerasuolo, Francesco Izzo, Luigi Buonaguro, Franco Maria Buonaguro
Summary: The expression and activity of TERT in the liver are closely associated with liver damage and the development of hepatocellular carcinoma (HCC). In addition to its role in telomere regulation, TERT has other oncogenic activities, making it a potential target for liver cancer therapy.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2022)
Article
Biotechnology & Applied Microbiology
Christian Sudfeld, Michal Hubacek, Daniel Figueiredo, Mihris I. S. Naduthodi, John van der Oost, Rene H. Wijffels, Maria J. Barbosa, Sarah D'Adamo
Summary: Nannochloropsis oceanica is a promising microalga platform, but current lipid yields are too low for economic feasibility. This study aimed to discover genes associated with increased neutral lipid content, with a promising mutant (HLM23) showing increased lipid content, enhanced photosynthetic performance, and no growth impairment. Transcriptome analysis revealed upregulation of genes related to fatty acid biosynthesis, glycolysis, and the Calvin-Benson-Bassham cycle in HLM23. Insights gained from this study can be used for future genetic engineering strategies to improve lipid productivity of Nannochloropsis.
METABOLIC ENGINEERING
(2021)
Article
Microbiology
Weiqing Zhang, Rui Deng, Weida Shi, Zheng Li, Robert M. Larkin, Qiuling Fan, Deqiang Duanmu
Summary: This study reveals the presence of an alternative bilin biosynthetic pathway independent of HMOX1 in the chloroplasts of Chlamydomonas cells. Bilins are crucial for maintaining chloroplast function, regulating chlorophyll biosynthesis, and supporting phototropic growth.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Microbiology
Jyotsna Chawla, Ilana Goldowitz, Jenna Oberstaller, Min Zhang, Camilla Valente Pires, Francesca Navarro, Lauriane Sollelis, Chengqi C. Q. Wang, Andreas Seyfang, Jeffrey Dvorin, Thomas D. D. Otto, Julian C. C. Rayner, Matthias Marti, John H. H. Adams
Summary: This article reports a study to identify genes associated with gametocyte development in the deadly malaria parasite Plasmodium falciparum. The study found a new set of genes that have not been implicated in gametocytogenesis before and demonstrated the potential of forward genetic screens in isolating genes impacting parasite sexual biology, which could lead to the discovery of new antimalarials.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biotechnology & Applied Microbiology
Kang Shen, Weiwei Hua, Shengjie Ge, Yu Mao, Yuexing Gu, Gaoyang Chen, Youwei Wang
Summary: A novel surface-enhanced Raman scattering (SERS) biosensor was developed to detect telomerase for early diagnosis and prognosis assessment of hepatocellular carcinoma (HCC). The biosensor showed excellent reproducibility, specificity, and sensitivity, and was validated using ELISA as the golden standard.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Desheng Chen, Yichao Lou, Jing Lu, Xuhui Fan, Qi Zhu, Hongcheng Sun
Summary: Through studying hepatocellular carcinoma, it was found that a signature consisting of four novel TMEM family genes (TMEM106C, TMEM201, TMEM164, and TMEM45A) can be used to predict patient survival status. High-risk patients have worse prognosis and more severe clinicopathological characteristics. The TMEMs signature plays an important role in cell-cycle and immune-related pathways. The tumor microenvironment of high-risk patients is immunosuppressive, while the low-risk group has more immune cell infiltration. The expression level of TMEMs signature is positively correlated with immune checkpoint expression. TMEM201, as a part of the TMEMs signature, can promote the progression of hepatocellular carcinoma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Medicine, Research & Experimental
Liwei Wu, Jiao Feng, Jingjing Li, Qiang Yu, Jie Ji, Jianye Wu, Weiqi Dai, Chuanyong Guo
Summary: Hepatocellular carcinoma is the most common primary liver malignancy with limited therapeutic options. Alterations in bile acids can affect hepatic metabolic balance and contribute to the pathogenesis of liver cancer. The gut microbiota plays a key role in promoting and developing liver cancer.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Review
Cell Biology
Mostafa K. Abd El-Aziz, Alyaa Dawoud, Caroline J. Kiriacos, Sherif Ashraf Fahmy, Nadia M. Hamdy, Rana A. Youness
Summary: The underlying mechanisms of hepatocellular carcinoma (HCC) are poorly understood, and the roles of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in HCC have been less investigated compared to coding genes and microRNAs. However, dysregulation of lncRNAs plays a significant role in HCC progression, making it an important research topic for potential diagnostic and prognostic biomarkers, as well as drug development.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Jana Tkacova, Giacomo Zara, Giuseppe Ianiri, Raffaello Castoria, Milan Certik, Ilaria Mannazzu
Summary: Red yeasts, such as Rhodotorula, were used as biocatalysts for the production of commercial secondary metabolites, including lipids and carotenoids. Mutants with impaired carotenoid biosynthesis were isolated using T-DNA insertional mutagenesis, showing altered metabolic characteristics and increased production of specific compounds. This study demonstrates the potential for enhanced production of secondary metabolites through manipulation of carotenoid biosynthesis in red yeasts.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Lena Goshayeshi, Sara Yousefi Taemeh, Nima Dehdilani, Mohammadreza Nasiri, Mohammad M. Ghahramani Seno, Hesam Dehghani
Summary: The study demonstrates the use of an RNA-guided piggyBac transposase and dual sgRNAs for site-directed integrations in the human ROSA26 safe harbor region. This methodology shows promise for targeting specific genomic regions, such as in cancer cells for inserting sequences into target regions or activating tumor suppressor genes.
Article
Oncology
Lisa von Wenserski, Christoph Schultheiss, Sarah Bolz, Simon Schliffke, Donjete Simnica, Edith Willscher, Helwe Gerull, Gerrit Wolters-Eisfeld, Kristoffer Riecken, Boris Fehse, Marcus Altfeld, Peter Nollau, Mascha Binder
Summary: SLAMF receptors were found to be important modulators of BCR signaling axis in CLL patients, potentially improving immune control by interfering with NK cells. The low expression of SLAMF1 and SLAMF7 was associated with decreased NK cell degranulation capacity and an unmutated CLL IGHV status.
Article
Biochemistry & Molecular Biology
Lea Isabell Schwarze, Tanja Sonntag, Stefan Wild, Sabrina Schmitz, Almut Uhde, Boris Fehse
Summary: The study introduces a novel strategy for HIV gene therapy targeting CD4(+)-T cells using CCR5-Uco-hetTALEN nuclease, which has been developed and optimised for GMP-compatible production. The automated mRNA electroporation protocol reliably produces high amounts of CCR5-edited CD4(+)-T cells suitable for clinical translation within 12 days.
Review
Biochemistry & Molecular Biology
Michael A. Morgan, Melanie Galla, Manuel Grez, Boris Fehse, Axel Schambach
Summary: Gene therapy can be used to treat monogenic disorders or enhance cells with new abilities. German research institutions have made significant contributions to the development of gene therapy, including designing vectors, conducting clinical trials, and assessing vector efficacy and safety.
Article
Virology
Manuela Mirow, Lea Isabell Schwarze, Boris Fehse, Kristoffer Riecken
Summary: The research team developed a novel codon-optimized Gibbon Ape Leukemia Virus envelope protein (coGALV-Env) that efficiently pseudotypes various types of viral vectors and mediates high-efficiency transduction in human T cells. This technology can be used not only in gene therapy but also can provide a significant cost advantage in the production of high-titer vector preparations.
Letter
Biophysics
Daniele Mannina, Anita Badbaran, Christine Wolschke, Evgeny Klyuchnikov, Maximilian Christopeit, Boris Fehse, Nicolaus Kroeger
BONE MARROW TRANSPLANTATION
(2022)
Article
Medicine, Research & Experimental
Anita Badbaran, Reiner K. Mailer, Christine Dahlke, Jannis Woens, Anahita Fathi, Sibylle C. Mellinghoff, Thomas Renne, Marylyn M. Addo, Kristoffer Riecken, Boris Fehse
Summary: Researchers have developed a highly sensitive dPCR method for quantifying ChAdOx1 nCoV-19 copies in vivo, which may help to elucidate the mechanisms behind severe complications associated with this vaccine.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Article
Oncology
Dawid Glow, Cecile L. Maire, Lea Isabell Schwarze, Katrin Lamszus, Boris Fehse
Summary: By targeting highly repetitive Alu sequences with CRISPR-to-kill (C2K) lentiviral vectors, effective killing of human cells and inhibition of cancer cell growth, including patient-derived glioblastoma cells resistant to high-dose radiation, were achieved, providing proof-of-concept for a novel treatment strategy overcoming common resistance mechanisms.
Article
Immunology
Kerri Hagemann, Kristoffer Riecken, Johannes M. Jung, Heike Hildebrandt, Stephan Menzel, Madeleine J. Bunders, Boris Fehse, Friedrich Koch-Nolte, Fabian Heinrich, Sven Peine, Julian Schulze zur Wiesch, Thomas T. Brehm, Marylyn M. Addo, Marc Luetgehetmann, Marcus Altfeld
Summary: In the context of COVID-19, the role of NK cells in the immune response has not been well understood. This study demonstrates that antibodies induced by SARS-CoV-2 infection and anti-SARS-CoV-2 vaccines can activate NK cells, leading to significant immune responses. These findings contribute to a better understanding of the role of NK cells in COVID-19.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Frauke Gotzhein, Tim Aranyossy, Lars Thielecke, Tanja Sonntag, Vanessa Thaden, Boris Fehse, Ingo Mueller, Ingmar Glauche, Kerstin Cornils
Summary: In this study, a murine model of HSCT was used to investigate the contribution of different hematological subpopulations to the reconstitution process and the impact of age on this process. The results showed that hematopoietic stem cells and multipotent progenitors played a major role in reconstitution, independent of age. The reconstitution patterns were stable in all age groups. These findings support the expansion of HSCT in older individuals as a promising strategy for treating hematological diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Adrin Dadkhah, Sebastian Georg Wicha, Nicolaus Kroeger, Alexander Mueller, Christoph Pfaffendorf, Maria Riedner, Anita Badbaran, Boris Fehse, Claudia Langebrake
Summary: This study developed a population pharmacokinetic (PopPK) model of busulfan and its metabolite sulfolane in patients with myelofibrosis. The model allowed for individual dose selection and improved understanding of busulfan's metabolic pathway in this patient population.
Article
Biochemistry & Molecular Biology
Lena-Marie Martin, Anne Kruchen, Boris Fehse, Ingo Mueller
Summary: Persistence of fetal cells in the mother's circulation has a beneficial effect on children with leukemia undergoing haploidentical hematopoietic stem cell transplantation. Maternal genetic factors and NK cells play important roles, but cytotoxicity is not solely determined by these factors.
Article
Hematology
Susanna Carolina Berger, Boris Fehse, Nuray Akyuz, Maria Geffken, Christine Wolschke, Dietlinde Janson, Nico Gagelmann, Marlene Luther, Dominic Wichmann, Christian Frenzel, Guenther Thayssen, Anna Alegiani, Anita Badbaran, Silke Zeschke, Judith Dierlamm, Nicolaus Kroger, Francis A. Ayuk
Summary: CD19-CAR T cell therapy can effectively treat B-cell malignancies, but may cause severe ICANS. The mechanisms of ICANS are not fully understood, and resistance to current therapies has been observed. In this study, we used digital PCR assays to monitor CD19-CAR T cell kinetics in CSF and blood of ICANS patients. We observed CAR T cell enrichment in CSF, even with intense corticosteroid-containing therapies. Longitudinal analysis showed a profound skewing of the T cell repertoire, with expansion of both CAR and non-CAR T cell clones. These findings suggest a role of therapy-refractory T cell clones in severe ICANS and prompt further research on CAR T cells.
Correction
Biochemistry & Molecular Biology
Lea Isabell Schwarze, Dawid Glow, Tanja Sonntag, Almut Uhde, Boris Fehse
Article
Biophysics
Marlene Luther, Frank Oliver Henes, Tatjana Zabelina, Radwan Massoud, Dietlinde Janson, Christine Wolschke, Evgeny Klyuchnikov, Nico Gagelmann, Boris Fehse, Gerhard Adam, Nicolaus Kroeger, Francis Ayuk
Summary: Splenomegaly is a characteristic of myelofibrosis, and the impact of spleen size on allo-HSCT outcome has been inconsistent due to different assessment methods. A retrospective analysis was conducted on 93 patients, revealing a strong correlation between spleen volume and length. Larger spleen size was associated with slower engraftment and higher risk of disease relapse. In the era of JAK inhibitors, larger spleen size reflects advanced disease and increased risk of relapse, but has no impact on non-relapse mortality and overall survival after allo-HSCT.
BONE MARROW TRANSPLANTATION
(2023)
Article
Biochemistry & Molecular Biology
Max Wichmann, Cecile L. Maire, Niklas Nuppenau, Moataz Habiballa, Almut Uhde, Katharina Kolbe, Tanja Schroeder, Katrin Lamszus, Boris Fehse, Dawid Glow
Summary: The CRISPR/Cas system has potential medical applications, but its clinical translation is hindered by the lack of safe and efficient vector systems. Virus-like particles (VLPs) have been introduced as promising vectors for CRISPR/Cas delivery. In this study, three types of retrovirus-based VLPs were compared, with enhanced egRVLPs showing the most efficient editing and minimal off-target activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)