Article
Biotechnology & Applied Microbiology
Joseph R. Owen, Sadie L. Hennig, Bret R. McNabb, Tamer A. Mansour, Justin M. Smith, Jason C. Lin, Amy E. Young, Josephine F. Trott, James D. Murray, Mary E. Delany, Pablo J. Ross, Alison L. Van Eenennaam
Summary: This study achieved high efficiency gene knock-ins in bovine zygotes using the HMEJ strategy, resulting in the birth of a phenotypically normal bull calf. Genomic analyses revealed allelic heterogeneity in the knock-in product, indicating a combination of repair and rearrangement mechanisms. Direct cytoplasmic injection of gRNA/Cas9 for targeted gene knock-ins shows potential, but further optimization is needed.
Review
Chemistry, Multidisciplinary
Alexander B. Cook, Paolo Decuzzi
Summary: Materials that respond to endogenous stimuli play a crucial role in enhancing spatiotemporal control in biomedical applications. These materials can be designed to undergo morphological or chemical changes in response to specific biological cues, offering promising opportunities for improving therapeutic efficacy and developing personalized healthcare systems. They can be engineered across different length scales to respond to endogenous signals such as enzymes, pH, glucose, and hold great potential for a wide range of applications.
Review
Chemistry, Multidisciplinary
Cheng Weng, Yong Leng Kelvin Tan, Wayne Gareth Koh, Wee Han Ang
Summary: Antimicrobial resistance is a serious and urgent threat to global public health, and the limited development of new drugs with alternative modes of action exacerbates this problem. Transition metal complexes can provide compounds with unique properties that are not easily accessible using pure organic scaffolds, replenishing the diminishing stockpile of drug candidates. This review highlights four emerging antibacterial strategies that harness the unique chemical properties of transition metal complexes, namely Trojan horse, triggered warhead release, new-to-nature chemistry, and biomimetic reactions.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Cell Biology
Zahra Labbaf, Kleio Petratou, Laura Ermlich, Wilko Backer, Katsiaryna Tarbashevich, Michal Reichman-Fried, Stefan Luschnig, Stefan Schulte-Merker, Erez Raz
Summary: Cell ablation is a crucial technique in the fields of developmental biology, tissue regeneration, and tissue homeostasis. The existing methods for inducing cell death have slow kinetics, which hinders the analysis of rapid events. To overcome this limitation, a new cell ablation system based on bacterial toxin/anti-toxin proteins has been developed, enabling rapid and cell-autonomous elimination of specific cell types and organs.
DEVELOPMENTAL CELL
(2022)
Article
Multidisciplinary Sciences
Shahin Eghbalsaied, Wilfried A. Kues
Summary: In this study, large plasmids containing the CRISPR/Cas9 system and a puromycin transgene were used to evaluate the efficiency of targeted integration. The inclusion of nocodazole and RNase HII during electroporation significantly improved the rate of high-fidelity repair events.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Multidisciplinary
Jieli Wei, Fanye Meng, Kwang-Su Park, Hyerin Yim, Julia Velez, Prashasti Kumar, Li Wang, Ling Xie, He Chen, Yudao Shen, Emily Teichman, Dongxu Li, Gang Greg Wang, Xian Chen, H. Umit Kaniskan, Jian Jin
Summary: PROTACs are a promising new therapeutic modality that utilize a limited number of E3 ligases for selective protein degradation. This study demonstrates that the KEAP1 E3 ligase can be utilized to generate highly selective PROTACs, expanding the toolbox for targeted protein degradation.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Seyoung Koo, Min-Goo Lee, Amit Sharma, Mingle Li, Xingcai Zhang, Kanyi Pu, Sung-Gil Chi, Jong Seung Kim
Summary: This study presents a molecular strategy that enhances the efficacy of photodynamic therapy (PDT) by utilizing ascorbate chemistry. The strategy targets cancer cells overexpressing glucose transporter 1 (GLUT1) and disrupts tumor redox homeostasis, leading to improved therapeutic responses. The approach shows promising synergistic effects in vitro and in vivo.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Multidisciplinary Sciences
Nayoung Ko, Joohyun Shim, Hyoung-Joo Kim, Yongjin Lee, Jae-Kyung Park, Kyungmin Kwak, Jeong-Woong Lee, Dong-Il Jin, Hyunil Kim, Kimyung Choi
Summary: Pig-to-human organ transplantation is a feasible solution for organ shortage. Engineered transgenic pigs with modified genes can potentially overcome immunological rejection. This study demonstrates the effectiveness of knocking-in transgenes into the GGTA1 locus and using the GGTA1 endogenous promoter for stable expression. The combination of CRISPR/Cas9 and the knock-in vector also improves targeting efficiency and nullifies the GalT gene. The transgenic pig developed in this study shows reduced immune reaction in vitro.
SCIENTIFIC REPORTS
(2022)
Review
Plant Sciences
Luyao Gao, Ning Hao, Tao Wu, Jiajian Cao
Summary: The quality of vegetables is facing new demands in terms of diversity and nutritional health. Scientists have been focusing on vegetable quality in breeding research, and gene manipulation technologies have been developed to improve commodity quality, flavor quality, and nutritional quality. This review summarizes recent studies on vegetable quality in major vegetable crops and analyzes the impact of modern agriculture.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Thomas D. Lewin, Ali A. Fouladi-Nashta, Peter W. H. Holland
Summary: This article investigates the role of ETCHbox genes in cattle and finds that ARGFX and LEUTX proteins can regulate the formation of blastocysts by upregulating genes normally expressed in blastocysts and downregulating genes associated with early development and undifferentiated cell state. The study also reveals overlapping functions of ARGFX and LEUTX in cattle, in contrast to their antagonistic roles in humans. Additionally, the research characterizes a mutant allele of ARGFX in cattle and shows that homozygous mutants are viable.
MOLECULAR BIOLOGY AND EVOLUTION
(2022)
Review
Chemistry, Physical
Jiahao Shi, Bin Ma, Yuhe Zhang, Haiyang Yong, Zhili Li, A. Sigen, Xiaobei Huang, Dezhong Zhou
Summary: Cancer therapy is a global challenge, but a variety of promising anticancer therapeutics have been developed. However, their direct administration often fails to achieve the desired efficacy due to low bioavailability and poor tissue selectivity. Polymers offer advantages for drug delivery, yet are generally poorly targeted to the tumor microenvironment (TME). The relatively lower acidity of the TME provides a specific trigger for the development of polymers for targeted delivery, and this article summarizes the strategies, mechanisms, and applications of acidity-sensitive polymers for delivering various anticancer therapeutics.
CHEMISTRY OF MATERIALS
(2023)
Article
Medicine, Research & Experimental
Rahimeh B. Atashgah, Amir Ghasemi, Mohammad Raoufi, Mohammad-Amin Abdollahifar, Steven Zanganeh, Hossein Nejadnik, Alieh Abdollahi, Shahriar Sharifi, Baltazar Lea, Miguel Cuerva, Mehdi Akbarzadeh, Carmen Alvarez-Lorenzo, Seyed Nasser Ostad, Andrea S. Theus, Doris L. LaRock, Christopher N. LaRock, Vahid Serpooshan, Rouzbeh Sarrafi, Ki-Bum Lee, Hojatollah Vali, Holger Schoenherr, Lisa Gould, Pablo Taboada, Morteza Mahmoudi
Summary: A multifunctional wound dressing has been developed by the research team to target multiple challenges in wound healing, accelerating the healing process and representing a promising alternative to current products.
MOLECULAR PHARMACEUTICS
(2021)
Review
Medicine, Research & Experimental
Mahere Rezazade Bazaz, Hesam Dehghani
Summary: This article provides a comprehensive overview of various gene knock-in methods using the CRISPR/Cas9 system in mammalian cells and discusses their relationship with DNA break repair pathways. Gene knock-in methods have broad applications in functional genomics and gene therapy, and researchers need to carefully choose the most suitable method based on specific circumstances.
Article
Multidisciplinary Sciences
Yan Jin, Yunkun Lu, Lianyu Lin, Chao Liu, Xiaojie Ma, Xi Chen, Ziyu Zhou, Zhensheng Hu, Jiaqi Pu, Guo Chen, Qian Deng, Liling Jiang, Yuhan Li, Yulong Zhao, Hao Wang, Junfen Fu, Wei Li, Saiyong Zhu
Summary: Chemistry-alone approach has been used to initiate pluripotency in somatic cells, but it has low efficiency and lacks understanding of the underlying mechanisms. This study reveals that the small molecule CD3254 activates the transcription factor RXRa and promotes chemical reprogramming in mice. The CD3254-RXRa-RNA exosome axis directly activates RNA exosome component genes, leading to the degradation of transposable element-associated RNAs and reduction of TE-mediated inflammation, ultimately promoting successful reprogramming.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Daisuke Arai, Yoichi Nakao
Summary: In this study, an optimized HDR-mediated knock-in method for mouse embryonic stem cells was developed, which significantly improved efficiency and minimized random integrations caused by NHEJ/MMEJ. The BiPoD method achieved efficient plasmid donor insertion and increased biallelic knock-in efficiency, providing a rapid and easy way to establish biallelic knock-in mESC lines.
SCIENTIFIC REPORTS
(2021)
Article
Biotechnology & Applied Microbiology
Michelle M. Halstead, Colin Kern, Perot Saelao, Ying Wang, Ganrea Chanthavixay, Juan F. Medrano, Alison L. Van Eenennaam, Ian Korf, Christopher K. Tuggle, Catherine W. Ernst, Huaijun Zhou, Pablo J. Ross
Article
Agriculture, Dairy & Animal Science
G. U. Maier, W. J. Love, B. M. Karle, S. A. Dubrovsky, D. R. Williams, J. D. Champagne, R. J. Anderson, J. D. Rowe, T. W. Lehenbauer, A. L. Van Eenennaam, S. S. Aly
JOURNAL OF DAIRY SCIENCE
(2020)
Article
Genetics & Heredity
Luiz Sergio Almeida Camargo, Joseph R. Owen, Alison L. Van Eenennaam, Pablo Juan Ross
FRONTIERS IN GENETICS
(2020)
Article
Biotechnology & Applied Microbiology
Joseph R. Owen, Sadie L. Hennig, Bret R. McNabb, Tamer A. Mansour, Justin M. Smith, Jason C. Lin, Amy E. Young, Josephine F. Trott, James D. Murray, Mary E. Delany, Pablo J. Ross, Alison L. Van Eenennaam
Summary: This study achieved high efficiency gene knock-ins in bovine zygotes using the HMEJ strategy, resulting in the birth of a phenotypically normal bull calf. Genomic analyses revealed allelic heterogeneity in the knock-in product, indicating a combination of repair and rearrangement mechanisms. Direct cytoplasmic injection of gRNA/Cas9 for targeted gene knock-ins shows potential, but further optimization is needed.
Article
Evolutionary Biology
Alison L. Van Eenennaam, Felipe De Figueiredo Silva, Josephine F. Trott, David Zilberman
Summary: The slow progress in the commercialization of genetically engineered livestock is mainly due to technical issues, the structure of livestock industries, lack of public research funding and investment, regulatory obstacles, and concern about public opinion. Researchers and developers have encountered difficulties in producing genetically engineered livestock. Delays in commercializing GE livestock beyond the normative 10-year evaluation period are associated with billions of dollars in opportunity costs and reduced global food security.
ANNUAL REVIEW OF ANIMAL BIOSCIENCES, VOL 9, 2021
(2021)
Article
Genetics & Heredity
Maci L. Mueller, John B. Cole, Natalie K. Connors, David J. Johnston, Imtiaz A. S. Randhawa, Alison L. Van Eenennaam
Summary: The study demonstrates that strong selection pressure on polled will be necessary due to the limited number of polled Australian Brahman bulls in order to significantly increase the number of polled animals in this population. Additionally, these scenarios illustrate how gene editing could be used as a tool to accelerate the development of high-genetic-merit homozygous polled sires in the Australian Brahman population to mitigate the trade-off of slower genetic gain associated with decreasing HORNED allele frequency.
FRONTIERS IN GENETICS
(2021)
Article
Multidisciplinary Sciences
Colin Kern, Ying Wang, Xiaoqin Xu, Zhangyuan Pan, Michelle Halstead, Ganrea Chanthavixay, Perot Saelao, Susan Waters, Ruidong Xiang, Amanda Chamberlain, Ian Korf, Mary E. Delany, Hans H. Cheng, Juan F. Medrano, Alison L. Van Eenennaam, Chris K. Tuggle, Catherine Ernst, Paul Flicek, Gerald Quon, Pablo Ross, Huaijun Zhou
Summary: Gene regulatory elements play a crucial role in animal genomes, with a core set of regulatory elements found to be functionally conserved across different species. These datasets offer a unique opportunity for comparative epigenomics and the agricultural research community.
NATURE COMMUNICATIONS
(2021)
Review
Genetics & Heredity
Jason C. Lin, Alison L. Van Eenennaam
Summary: Introducing genome editing reagents into mammalian zygotes via electroporation provides a simpler and more streamlined approach compared to traditional methods. Studies have examined parameters for mouse and rat zygotes, with limited reports on livestock zygotes. Delivery of genome editing reagents via electroporation can help reduce mosaicism, especially in large livestock species.
FRONTIERS IN GENETICS
(2021)
Review
Agriculture, Dairy & Animal Science
A. L. Van Eenennaam, S. J. Werth
Summary: Discussions on sustainability often involve competing goals, leading to conflicting outcomes. The role of livestock in sustainable diets is contentious, and the emerging market for alternative meats aims to reduce GHG emissions and animal agriculture, but may overlook the nutritional importance of ASF. Technological innovations are crucial for improving the efficiency of animal source, plant source, and cultured meat production in order to meet future demand sustainably and counteract misinformation that may hinder global food security.
Article
Veterinary Sciences
Deepak, Sharif S. Aly, William J. Love, Patricia C. Blanchard, Beate Crossley, Alison L. Van Eenennaam, Terry W. Lehenbauer
Summary: The study estimated the association of BRD risk factors in pre-weaned dairy calves in California. Female calves were more negatively impacted by failure of passive immunity transfer compared to male calves. Different pathogens had varying odds ratios, with Mannheimia haemolytica and Pasteurella multocida showing high associations with BRD. Age, sex, immune status, and pathogens all played a role in BRD occurrence in pre-weaned dairy calves.
PREVENTIVE VETERINARY MEDICINE
(2021)
Article
Multidisciplinary Sciences
Sadie L. Hennig, Joseph R. Owen, Jason C. Lin, Bret R. McNabb, Alison L. Van Eenennaam, James D. Murray
Summary: Dehorning in cattle using CRISPR-Cas9 gene editing to remove a 133 bp region including a 10 bp sequence resulted in embryos with mutations, but not necessarily the desired polled phenotype. The timing of injection post-insemination and the use of synthetic gRNAs both affected the deletion rate in the embryos, highlighting the complexity of genetic factors influencing horn development in cattle.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Sadie L. Hennig, Bret R. McNabb, Josephine F. Trott, Alison L. Van Eenennaam, James D. Murray
Summary: A long intergenic non-coding RNA (lincRNA#1) is highly expressed in the horn bud region of polled bovine fetuses, but its absence alone does not result in a hornless phenotype.
SCIENTIFIC REPORTS
(2022)
Article
Biochemical Research Methods
Carolyn J. Lawrence-Dill, Robyn L. Allscheid, Albert Boaitey, Todd Bauman, Edward S. Buckler, Jennifer L. Clarke, Christopher Cullis, Jack Dekkers, Cassandra J. Dorius, Shawn F. Dorius, David Ertl, Matthew Homann, Guiping Hu, Mary Losch, Eric Lyons, Brenda Murdoch, Zahra-Katy Navabi, Somashekhar Punnuri, Fahad Rafiq, James M. Reecy, Patrick S. Schnable, Nicole M. Scott, Moira Sheehan, Xavier Sirault, Margaret Staton, Christopher K. Tuggle, Alison Van Eenennaam, Rachael Voas
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Julie A. Finzel, Austin R. Brown, Roselle C. Busch, Morgan P. Doran, John M. Harper, Daniel K. Macon, Rebecca K. Ozeran, Morgan R. Stegemiller, Karissa Isaacs, Alison Van Eenennaam
Summary: Despite being available for over a decade, adoption of electronic identification ear tags (EID) and DNA testing among commercial range sheep producers in the Western United States has been low. This project involved collaboration with five California sheep producers to demonstrate the potential of these technologies in improving flock health and reproductive management.