Review
Immunology
Hager Mohamed, Theodore Gurrola, Rachel Berman, Mackenzie Collins, Ilker K. Sariyer, Michael R. Nonnemacher, Brian Wigdahl
Summary: HIV-1 infection is a global health burden, and current drug therapies face challenges. Novel anti-HIV-1 therapies targeting CCR5 have shown promise in preventing infection and are included in gene editing techniques, CCR5 blockade using antibodies or antagonists, or combinations of both.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Engineering, Biomedical
Nikita Mikhailov, Riikka H. Hamalainen
Summary: Mitochondria are not only the energy factories of eukaryotic cells, but also have various signaling and metabolic functions. Mutations in the mitochondrial genome are a significant contributor to human disease. Modulating the ratio between healthy and mutant mtDNA in patients' cells offers a potential therapeutic option for mtDNA diseases.
ANNALS OF BIOMEDICAL ENGINEERING
(2022)
Article
Multidisciplinary Sciences
Ranjeet Maurya, Aparna Swaminathan, Uzma Shamim, Smriti Arora, Pallavi Mishra, Aakarshan Raina, Varsha Ravi, Bansidhar Tarai, Sandeep Budhiraja, Rajesh Pandey
Summary: The emergence of multiple SAR-CoV-2 variants during the COVID-19 pandemic has led to an increased understanding of the host-immune kinetics associated with these variants. A longitudinal investigation revealed a robust antiviral response in Omicron infection, which was largely absent in the Pre-VOC and Delta waves. The study also highlighted differential protein-protein interactions and gene expression patterns, particularly in relation to zinc finger proteins, that contribute to the immune response.
Article
Cell Biology
Bin Yang, Haiyu Tang, Nan Wang, Jian Gu, Qin Wang
Summary: Abnormal hypermethylation of the ZNF334 gene, which downregulates its expression, was detected in CRC tissues. TET1 was identified to be involved in regulating the methylation level of ZNF334. A constructed targeted demethylation system successfully upregulated ZNF334 expression and inhibited CRC growth.
CELL DEATH & DISEASE
(2023)
Article
Biotechnology & Applied Microbiology
Jiyeon Kweon, Hye-Yeon Hwang, Haesun Ryu, An-Hee Jang, Daesik Kim, Yongsub Kim
Summary: Researchers developed a method using prime editor 2 nuclease (PE2 nuclease) and paired pegRNA to achieve programmable chromosomal translocations and inversions. They successfully introduced DNA recombination and precise chromosomal translocations in human cells. This method can be used to create cancer-associated translocations and inversions as well as for disease modeling or gene therapy.
Article
Chemistry, Multidisciplinary
Subhra Mandal, Shawnalyn W. Sunagawa, Pavan Kumar Prathipati, Michael Belshan, Annemarie Shibata, Christopher J. Destache
Summary: A targeted nanoformulation was designed to block CCR5 expression on T cells and inhibit HIV replication. The nanoformulation showed improved binding affinity to CCR5 and high binding affinity to different types of CCR5+ cells. Short-term prophylaxis study demonstrated that the nanoformulation induced a protective immune phenotype, which could contribute to achieving HIV functional cure.
Article
Biochemistry & Molecular Biology
Koollawat Chupradit, Wannisa Khamaikawin, Supachai Sakkhachornphop, Chaniporn Puaninta, Bruce E. Torbett, Suparerk Borwornpinyo, Suradej Hongeng, Methichit Wattanapanitch, Chatchai Tayapiwatana
Summary: The study demonstrates the efficacy and safety of using 2LTRZFP in human CD34(+) HSPCs for gene therapy in HIV-1-infected individuals. The 2LTRZFPmCherry-transduced macrophages showed normal function and phenotype, and exhibited resistance to HIV-1 integration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biotechnology & Applied Microbiology
Hiroshi Hisano, Robert E. Hoffie, Fumitaka Abe, Hiromi Munemori, Takakazu Matsuura, Masaki Endo, Masafumi Mikami, Shingo Nakamura, Jochen Kumlehn, Kazuhiro Sato
Summary: Mutants with targeted mutations in Qsd1 and Qsd2 were created using Cas9-induced mutagenesis in this study. The mutants showed strong repression of germination, with Qsd1 germination being promoted by treatment with hydrogen peroxide and the block of germination alleviated by exposure to cold temperatures.
PLANT BIOTECHNOLOGY JOURNAL
(2022)
Article
Medicine, Research & Experimental
Shasha Li, Leo Holguin, John C. Burnetti
Summary: This preclinical study evaluated the efficacy of disrupting the CCR5 and CXCR4 genes simultaneously to create broad HIV resistance. The results showed that CRISPR-mediated disruption of CCR5 and CXCR4 effectively reduced surface expression of co-receptors, leading to resistance against different strains of HIV. However, disrupting both CCR5 and CXCR4 may affect the engraftment of CD4(+) T cells in the bone marrow.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Cell Biology
Weilin Pu, Fei Qian, Jing Liu, Keke Shao, Feng Xiao, Qin Jin, Qingmei Liu, Shuai Jiang, Rui Zhang, Jun Zhang, Shicheng Guo, Jianfeng Zhang, Yanyun Ma, Shaoqing Ju, Weifeng Ding
Summary: The study suggests that ESR1 and ZNF132 may have better predictive capabilities for early diagnosis of CRC compared to SEPT9, especially in CRC patients with KRAS mutations.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Chemistry, Analytical
Koollawat Chupradit, Weeraya Thongkum, On-anong Juntit, Kanokporn Sornsuwan, Chatchai Tayapiwatana
Summary: Protein-DNA interactions play essential roles in cellular processes. Utilizing Biolayer Interferometry (BLI), this study determined the kinetic binding of 2LTRZFP and demonstrated its inhibitory effect on HIV-1 integration. The findings revealed high affinity binding of 2LTRZFP to ds2LTR target and no off-target effects on the human genome, supporting the potential use of 2LTRZFP in HIV-1 gene therapy.
Article
Engineering, Biomedical
Pedro Silva-Pinheiro, Christian D. Mutti, Lindsey Van Haute, Christopher A. Powell, Pavel A. Nash, Keira Turner, Michal Minczuk
Summary: The study developed a DNA editor called MitoKO, which can precisely eliminate each protein-coding gene in the mouse mitochondrial genome. MitoKO was used to generate knockout cells with high homoplasmy levels in vitro and a mouse model with high heteroplasmy levels and no off-target edits. This tool will aid in the comprehensive investigation of mtDNA-related pathways and the creation of clinically relevant in vivo models of mtDNA dysfunction.
NATURE BIOMEDICAL ENGINEERING
(2023)
Article
Oncology
Xixi Zhou, Rachel M. Speer, Lindsay Volk, Laurie G. Hudson, Ke Jian Liu
Summary: Arsenic exposure at environmentally relevant levels can enhance the carcinogenic effect of other agents, such as UV radiation, by inhibiting DNA repair. This review highlights the recent advances in understanding the mechanisms of arsenic carcinogenesis, including DNA damage induction and ROS generation, particularly focusing on how arsenic inhibits DNA repair through interactions with sensitive zinc finger DNA repair proteins.
SEMINARS IN CANCER BIOLOGY
(2021)
Article
Biochemical Research Methods
Meghan W. Dukes, Elizabeth A. Bajema, Tyler J. Whittemore, Robert A. Holmgren, Thomas J. Meade
Summary: A polyethyleneimine-functionalized graphene oxide nanoconjugate (GOPEI) was developed to deliver a CoGli complex that targets Gli specifically, resulting in a 17-fold improvement in inhibiting migration of basal cell carcinoma (BCC) cells compared to small-molecule Gli inhibitor.
BIOCONJUGATE CHEMISTRY
(2022)
Review
Agronomy
Hiroshi Hisano, Fumitaka Abe, E. Robert Hoffie, Jochen Kumlehn
Summary: The recent development of customizable endonucleases has significantly advanced genetic engineering, providing unprecedented precision and efficiency for targeted gene modifications. Among these technologies, RNA-guided CRISPR-associated Cas endonucleases stand out as the most powerful tool for genome editing applications.
Article
Multidisciplinary Sciences
Eunseon Ahn, Koichi Araki, Masao Hashimoto, Weiyan Li, James L. Riley, Jeanne Cheung, Arlene H. Sharpe, Gordon J. Freeman, Bryan A. Irving, Rafi Ahmed
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2018)
Review
Immunology
Gloria B. Kim, Kristen Hege, James L. Riley
FRONTIERS IN IMMUNOLOGY
(2019)
Article
Biotechnology & Applied Microbiology
Colby R. Maldini, Kevin Gayout, Rachel S. Leibman, Derrick L. Dopkin, Joshua P. Mills, Xiaochuan Shan, Joshua A. Glover, James L. Riley
Article
Hematology
Blake J. Rust, Leslie S. Kean, Lucrezia Colonna, Katherine E. Brandenstein, Nikhita H. Poole, Willimark Obenza, Mark R. Enstrom, Colby R. Maldini, Gavin Ellis, Christine M. Fennessey, Meei-Li Huang, Brandon F. Keele, Keith R. Jerome, James L. Riley, Hans-Peter Kiem, Christopher W. Peterson
Article
Biochemistry & Molecular Biology
Mohamed Abdel-Mohsen, Douglas Richman, Robert F. Siliciano, Michel C. Nussenzweig, Bonnie J. Howell, Javier Martinez-Picado, Nicolas Chomont, Katharine J. Bar, Xu G. Yu, Mathias Lichterfeld, Jose Alcami, Daria Hazuda, Frederic Bushman, Janet D. Siliciano, Michael R. Betts, Adam M. Spivak, Vicente Planelles, Beatrice H. Hahn, Davey M. Smith, Ya-Chi Ho, Maria J. Buzon, Christian Gaebler, Mirko Paiardini, Qingsheng Li, Jacob D. Estes, Thomas J. Hope, Jay Kostman, Karam Mounzer, Marina Caskey, Lawrence Fox, Ian Frank, James L. Riley, Pablo Tebas, Luis J. Montaner
Article
Biochemistry & Molecular Biology
Colby R. Maldini, Daniel T. Claiborne, Ken Okawa, Tao Chen, Derrick L. Dopkin, Xiaochuan Shan, Karen A. Power, Radiana T. Trifonova, Katharine Krupp, Meredith Phelps, Vladimir D. Vrbanac, Serah Tanno, Timothy Bateson, George J. Leslie, James A. Hoxie, Christian L. Boutwell, James L. Riley, Todd M. Allen
Article
Immunology
Yuqi Zhou, Colby R. Maldini, Julie Jadlowsky, James L. Riley
Summary: A successful strategy for curing HIV may involve a durable and potent T-cell police force to eliminate any remaining virus. The best way to restore HIV-specific T-cell activity before initiating treatment is currently unclear.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Review
Genetics & Heredity
Gavin I. Ellis, Neil C. Sheppard, James L. Riley
Summary: Genetically engineered T cell immunotherapies have shown remarkable success in treating B cell acute lymphoblastic leukemia by using a patient's own T cells to target cancer cells. However, more complex levels of genetic regulation will be necessary to ensure safety and efficacy in future therapies.
NATURE REVIEWS GENETICS
(2021)
Article
Hematology
Zachary Davis, Martin Felices, Todd Lenvik, Sujan Badal, Joshua T. Walker, Peter Hinderlie, James L. Riley, Daniel A. Vallera, Bruce R. Blazar, Jeffrey S. Miller
Summary: The study showed that functional PD-1 is expressed on resting human NK cells in healthy individuals and reconstituting NK cells early after allo-HSCT. Blocking PD-1 on resting NK cells enhanced their function against PD-L1-expressing tumor lines, indicating the potential for PD-1 blockade in enhancing NK cell-mediated antitumor control.
Editorial Material
Cell Biology
Divanshu Shukla, James L. Riley
Article
Medicine, Research & Experimental
Pablo Tebas, Julie K. Jadlowsky, Pamela A. Shaw, Lifeng Tian, Erin Esparza, Andrea L. Brennan, Sukyung Kim, Soe Yu Naing, Max W. Richardson, Ashley N. Vogel, Colby R. Maldini, Hong Kong, Xiaojun Liu, Simon F. Lacey, Anya M. Bauer, Felicity Mampe, Lee P. Richman, Gary Lee, Dale Ando, Bruce L. Levine, David L. Porter, Yangbing Zhao, Don L. Siegel, Katharine J. Bar, Carl H. June, James L. Riley
Summary: By infusing CCR5 gene-edited CD4(+) T cells, delay of HIV viral rebound and enhancement of HIV-specific immune responses can be achieved, aiding HIV cure strategies. However, only a minority of patients showed signs of viral replication control, accompanied by significant restoration of HIV-specific CD8(+) T cell responses.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Immunology
Mary M. Addison, Gavin Ellis, George J. Leslie, Noah B. Zawadzky, James L. Riley, James A. Hoxie, Laurence C. Eisenlohr
Summary: Activated human T(C)(D4)(+) cells not only function as mediators of immune responses in controlling HIV-1 infection but also act as APCs, expressing MHC II and effectively presenting HIV-1-induced immunodominant epitopes as well as endogenously produced antigens.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Megan M. Wyatt, Logan W. Huff, Michelle H. Nelson, Lillian R. Neal, Andrew R. Medvec, Guillermo O. Rangel Rivera, Aubrey S. Smith, Amalia M. Rivera Reyes, Hannah M. Knochelmann, James L. Riley, Gregory B. Lesinski, Chrystal M. Paulos
Summary: IL-17-producing antigen-specific human T cells show strong antitumor activity in mice, but refinement is needed for clinical use. The influence of TCR and costimulation signal strength on Th17 immunity is unclear. We found that reducing TCR/costimulation signal strength altered Th17 phenotype and stimulated cells produced more cytokines. Lower signal strength Th17 cells were less reliant on glucose and more effective at clearing human mesothelioma.
Article
Hematology
Zhenguo Zi, Shujuan Du, Liming Zhang, Yuebo Wang, Ling Ding, Chongqi Zhang, Huanyu Wang, Jan Pawlicki, Yuan Cai, Yazhou Yao, Feng Zhou, Yin Tong, James L. Riley, Qiliang Cai, Xiaojing Ma, Fang Wei
Summary: GOLM1 is significantly upregulated in ALK-positive anaplastic large cell lymphoma (ALCL) and plays a critical role in promoting cell growth and viability. It directly interacts with B-cell lymphoma-extra large protein, prolongs its stability, and suppresses apoptosis. GOLM1 may serve as a potential biomarker and therapeutic target in ALK-induced hematological malignancies.
Article
Biochemical Research Methods
Gavin I. Ellis, Mosha Z. Deng, Delaine W. Winn, Kimberly E. Coker, Divanshu Shukla, Vijay Bhoj, Michael C. Milone, Raimon Duran-Struuck, James L. Riley
Summary: This study optimized the manufacturing of CAR Tregs and generated highly suppressive CAR Tregs in non-human primates for use in a pre-clinical, large animal model of transplant tolerance.