Article
Chemistry, Multidisciplinary
Carly K. Schissel, Somesh Mohapatra, Justin M. Wolfe, Colin M. Fadzen, Kamela Bellovoda, Chia-Ling Wu, Jenna A. Wood, Annika B. Malmberg, Andrei Loas, Rafael Gomez-Bombarelli, Bradley L. Pentelute
Summary: The study demonstrates that deep learning can decipher design principles to generate highly active biomolecules, such as Mach proteins, which are capable of delivering antisense cargo efficiently without toxicity in mice. This approach combines high-throughput experimentation with a deep-learning method inspired by directed evolution, representing molecular structures as topological fingerprints.
Article
Multidisciplinary Sciences
Taiki Tsurusaki, Kazuki Sato, Hiroki Imai, Kunihiro Hirai, Daisuke Takahashi, Takeshi Wada
Summary: Phosphorodiamidate morpholino oligonucleotides (PMOs) are a promising type of antisense oligonucleotides, but their challenging synthesis makes them difficult to access. This research presents an efficient synthetic approach for PMOs using the H-phosphonate approach. The use of phosphonium-type condensing reagents significantly reduced coupling times compared with the current synthetic approach. This approach would facilitate the large-scale synthesis of PMOs and accelerate their popularity and accessibility as a next-generation therapy.
SCIENTIFIC REPORTS
(2023)
Article
Microbiology
Asako Tan, Senthil Murugapiran, Alaya Mikalauskas, Jeff Koble, Drew Kennedy, Fred Hyde, Victor Ruotti, Emily Law, Jordan Jensen, Gary P. Schroth, Jean M. Macklaim, Scott Kuersten, Brice LeFrancois, Daryl M. Gohl
Summary: The microbiota in the human gut and other tissues are dynamic and vary in composition and function over time and between individuals. Gene expression measurements can provide insights into the microbiome, but removing microbial ribosomal RNA (rRNA) efficiently and unbiasedly is challenging. In this study, a probe set is described that effectively removes rRNA from complex human-associated microbial communities. Through an iterative design process, the probe set can be optimized to deplete rRNA from various human microbiome samples. The successful rRNA depletion allows for efficient characterization of taxonomic and functional profiles, including during the development of the human gut microbiome. The enzymatic rRNA depletion probes described here provide a powerful tool for studying the transcriptional dynamics and function of the human microbiome.
Article
Chemistry, Organic
Atanu Ghosh, Masaaki Akabane-Nakata, Jayanta Kundu, Joel M. Harp, Mimouna Madaoui, Martin Egli, Muthiah Manoharan, Surajit Sinha
Summary: We synthesized piperidino nucleoside phosphoramidates functionalized with uracil, cytosine, guanine, and adenine and incorporated them into oligomers. High-performance liquid chromatography analyses showed that a phosphorodiamidate piperidino oligomer (PPO) is more lipophilic than a phosphorodiamidate morpholino oligomer (PMO) with the same tetrameric sequence. The PMO containing piperidino residues formed duplexes with both DNA and RNA, while the PPO exhibited higher stability at endosomolytic pH and higher hydrophobicity than the PMO.
Article
Agriculture, Dairy & Animal Science
Hanwen Gu, Yu H. Sun, Xin Zhiguo Li
Summary: Deep sequencing of RNA has revolutionized transcriptome research, but efficiently enriching mRNA species is a challenge. This study introduces a cost-effective method for depleting rRNAs, using chickens as a model species. The method not only removes rRNAs for RNA-seq library construction, but also for ribosome profiling.
Article
Biochemistry & Molecular Biology
Chiara Pacelli, Alice Rossi, Michele Milella, Teresa Colombo, Loredana Le Pera
Summary: Precision medicine in oncology has made significant progress, but many cancer driver genes are still difficult to target with drugs. RNA-based methods, such as antisense oligonucleotides (ASOs), can induce targeted exon skipping (ES) and provide a promising alternative. This work presents a comprehensive computational procedure for developing ES-based cancer treatments, including target-exon selection, in silico prediction of ES products, and identification of optimal ASOs for experimental validation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Jakob Jung, Linda Popella, Phuong Thao Do, Patrick Pfau, Joerg Vogel, Lars Barquist
Summary: MASON is a web server for designing PNAs that target bacterial mRNAs. It predicts off-target effects and provides critical sequence attributes and potential off-target sites. Experiments showed that PNAs may have wider off-target effects than anticipated. The off-target assessment provided by MASON can improve the design of specific PNAs and other ASOs.
Article
Chemistry, Multidisciplinary
Chengxi Li, Alex J. Callahan, Kruttika S. Phadke, Bryan Bellaire, Charlotte E. Farquhar, Genwei Zhang, Carly K. Schissel, Alexander J. Mijalis, Nina Hartrampf, Andrei Loas, David E. Verhoeven, Bradley L. Pentelute
Summary: This study reports an efficient technology that utilizes a fully automated fast-flow instrument to manufacture cell-penetrating peptide-conjugated peptide nucleic acids (PPNAs), which improves cellular uptake. The synthesized PPNAs showed improved activity in splice-correction and antiviral assays. This technology has the potential to be used for further investigation of PPNA candidates as antiviral agents.
ACS CENTRAL SCIENCE
(2022)
Article
Materials Science, Biomaterials
Taishun Hu, Xiyu Gong, Xinli Liu, Hui Xu, Fangfang Zhou, Songwen Tan, Yongju He
Summary: Multifunctional nanoparticles (MSN-TPP/BNA-DPA) have been developed to target mitochondria for copper-depletion therapy and deliver anticancer drugs for chemotherapy. These nanoparticles are constructed by conjugating a fluorophore (BNA), a copper-depriving moiety (DPA), and a mitochondrial targeting ligand (TPP) on the surface of mesoporous silica nanoparticles (MSN). The use of BNA-DPA enables visualization of copper-depletion through quenching of green fluorescence upon copper binding. Therapeutically, mitochondria-targeted copper-depletion causes mitochondria damage, oxidative stress, and reduced ATP production to induce cancer cell death.
JOURNAL OF MATERIALS CHEMISTRY B
(2023)
Article
Chemistry, Multidisciplinary
Wes Brown, Anirban Bardhan, Kristie Darrah, Michael Tsang, Alexander Deiters
Summary: The study reveals that light-activated circular morpholino oligonucleotides can be used to conditionally control microRNA function and study their role in zebrafish embryo development. Precise spatial and temporal control over microRNA function was achieved through irradiation, providing insights into the cell populations and developmental timepoints involved in each process.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Michael R. Erdos, Wayne A. Cabral, Urraca L. Tavarez, Kan Cao, Jelena Gvozdenovic-Jeremic, Narisu Narisu, Patricia M. Zerfas, Stacy Crumley, Yoseph Boku, Gunnar Hanson, Dan V. Mourich, Ryszard Kole, Michael A. Eckhaus, Leslie B. Gordon, Francis S. Collins
Summary: Using an antisense peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) to block pathogenic splicing of mutant transcripts has shown promising results in reducing progerin levels and extending lifespan in a mouse model of Hutchinson-Gilford progeria syndrome.
Article
Physics, Multidisciplinary
Caiyou Zhao, Xinhao Zhang, Ping Wang, Nachao Wei, Mingjing Geng, Qingmin Hui, Qi Yu, Kangjia Qiao, Tao Lu
Summary: A modular design optimization method is proposed for acoustic metamaterial cells. By using the objective function of an arbitrary noise source and the constraints of the application, the method ensures satisfying the targeted noise attenuation. The core algorithm combines the generalized particle swarm algorithm and wave finite element method for structural and targeted optimization. The output includes the optimized metamaterial cell and its sound barrier structure. Acoustic testing of a 3D-printed prototype verifies the desired noise reduction performance. The simulation and experimental results demonstrate that the designed acoustic metamaterial can effectively block the target noise band and has advantages in design efficiency, lightweight, and noise attenuation.
ANNALEN DER PHYSIK
(2023)
Article
Chemistry, Multidisciplinary
Guobin Qi, Xianglong Liu, Leilei Shi, Jiahao Zhuang, Bin Liu
Summary: This study reports a platform that uses bacteria as templates to synthesize polymers containing guanidinium groups, which can selectively remove pathogenic bacteria without significant damage to microbial communities.
ADVANCED MATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Gwangjun Go, Hyeong-Woo Song, Minghui Nan, Junhyeok Lee, Seokjae Kim, Jong-Oh Park, Eunpyo Choi
Summary: A chitosan-based biodegradable microrobot with optimized structural design and X-ray imaging for targeted vessel chemoembolization is reported. The microrobot takes into account its magnetizability and stackability in blood vessels. The optimized microrobot is biocompatible, biodegradable, thrombogenic, magnetically targetable, and drug-loadable, as demonstrated both in vitro and in a blood vessel phantom. X-ray imaging of the gold nanoparticle-attached microrobots compares well with using commercial iodinated contrast materials.
ADVANCED FUNCTIONAL MATERIALS
(2023)
Review
Chemistry, Multidisciplinary
Hao Cui, Xinying Zhu, Shuyue Li, Peipei Wang, Jianping Fang
Summary: The potential therapeutic application of oligonucleotides that selectively suppress target genes through antisense and RNA interference mechanisms has attracted widespread attention, with a focus on liver-targeted delivery using N-acetylgalactosamine (GalNAc) ligands. Recent progress in the field of GalNAc conjugates for improving cellular uptake and tissue-specific delivery has shown promising results in preclinical and clinical trials.
Meeting Abstract
Biophysics
Maiwase Tembo, Rachel E. Bainbridge, Anne E. Carlson
BIOPHYSICAL JOURNAL
(2019)
Meeting Abstract
Biophysics
Katherine L. Wozniak, Wesley A. Phelps, Miler T. Lee, Anne E. Carlson
BIOPHYSICAL JOURNAL
(2019)
Editorial Material
Physiology
Maiwase Tembo, Anne E. Carlson
JOURNAL OF GENERAL PHYSIOLOGY
(2019)
Review
Biochemistry & Molecular Biology
Katherine L. Wozniak, Anne E. Carlson
MOLECULAR REPRODUCTION AND DEVELOPMENT
(2020)
Article
Biochemistry & Molecular Biology
Maiwase Tembo, Katherine L. Wozniak, Rachel E. Bainbridge, Anne E. Carlson
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Editorial Material
Multidisciplinary Sciences
Anne E. Carlson
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Editorial Material
Biochemistry & Molecular Biology
Rachel E. Bainbridge, Anne E. Carlson
TRENDS IN BIOCHEMICAL SCIENCES
(2019)
Article
Biochemistry & Molecular Biology
Katherine L. Wozniak, Rachel E. Bainbridge, Dominique W. Summerville, Maiwase Tembo, Wesley A. Phelps, Monica L. Sauer, Bennett W. Wisner, Madelyn E. Czekalski, Srikavya Pasumarthy, Meghan L. Hanson, Melania B. Linderman, Catherine H. Luu, Madison E. Boehm, Steven M. Sanders, Katherine M. Buckley, Daniel J. Bain, Matthew L. Nicotra, Miler T. Lee, Anne E. Carlson
Editorial Material
Biology
Kayla M. Komondor, Anne E. Carlson
Correction
Biochemistry & Molecular Biology
Wesley A. Phelps, Anne E. Carlson, Miler T. Lee
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Maiwase Tembo, Rachel E. Bainbridge, Crystal Lara-Santos, Kayla M. Komondor, Grant J. Daskivich, Jacob D. Durrant, Joel C. Rosenbaum, Anne E. Carlson
Summary: This study investigates the interaction between TMEM16A channel and the membrane lipid phosphatidylinositol 4,5-bisphosphate (PI(4,5)P-2). The findings show that only lipids containing a phosphate at the 40 position effectively recover TMEM16A currents. These findings improve our understanding of how PI(4,5)P-2 binds to and potentiates TMEM16A channels.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Meeting Abstract
Biophysics
Maiwase Tembo, Anne E. Carlson
BIOPHYSICAL JOURNAL
(2020)
Meeting Abstract
Biophysics
Rachel E. Bainbridge, Katherine Wozniak, Wesley A. Phelps, Steven M. Sanders, Matthew L. Nicotra, Miler T. Lee, Anne E. Carlson
BIOPHYSICAL JOURNAL
(2020)
Meeting Abstract
Biophysics
Maiwase Tembo, Anne E. Carlson
BIOPHYSICAL JOURNAL
(2018)