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Drug discovery companies are customizing ChatGPT: here’s how
Neil SavageÂÂ
Drug pipeline 1Q23 � Everything everywhere all over the place
John HodgsonÂÂ
Drug pipeline 1Q23 � Everything everywhere all over the place
John HodgsonÂÂ
The scverse project provides a computational ecosystem for single-cell omics data analysis
Isaac Virshup, Danila Bredikhin, Lukas Heumos, Giovanni Palla, Gregor Sturm, Adam Gayoso, Ilia Kats, Mikaela Koutrouli, Scverse Community, Bonnie Berger, Dana Pe’er, Aviv Regev, Sarah A. Teichmann, Francesca Finotello, F. Alexander Wolf, Nir Yosef, Oliver Stegle & Fabian J. TheisÂ
Challenges and solutions to advancing health equity with medical devices
Kushal T. Kadakia, Vinay K. Rathi, Reshma Ramachandran, James L. Johnston, Joseph S. Ross & Sanket S. DhruvaÂ
Who counts as an inventor? Seniority and gender in 430,000 biomedical inventor–researcher teams
Anoop Manjunath, Nathan Kahrobai, Jaya Manjunath, Angelina Seffens, Arya Gowda, Rohaan Umbarkar, Esha Umbarkar, James Y. Zou & Ishan KumarÂ
Protein sequences absent in nature generated with diffusion model
Jared B. FudgeÂÂ
Bespoke protein delivery via bacterial injection systems
Jared B. FudgeÂÂ
Transposon–gene chimeras move up as cancer epitopes
Jared B. FudgeÂÂ
Rapid mining of (meta)genomic biodiversity by repurposing CRISPRi for positive selection
Healing chronic wounds with a wireless smart bandage with integrated sensors and stimulators
Profiling chromatin–protein crosstalk at locus resolution in single cells
High-throughput retrieval of target sequences from complex clone libraries using CRISPRi
Ján Burian, Vincent K. Libis, Yozen A. Hernandez, Liliana Guerrero-Porras, Melinda A. Ternei & Sean F. BradyÂ
doi : 10.1038/s41587-022-01531-8
The capture of metagenomic DNA in large clone libraries provides the opportunity to study microbial diversity that is inaccessible using culture-dependent methods. In this study, we harnessed nuclease-deficient Cas9 to establish a CRISPR counter-selection interruption circuit (CCIC) that can be used to retrieve target clones from complex libraries. Combining modern sequencing methods with CCIC cloning allows for rapid physical access to the genetic diversity present in natural ecosystems.
Time-tagged ticker tapes for intracellular recordings
Dingchang Lin, Xiuyuan Li, Eric Moult, Pojeong Park, Benjamin Tang, Hao Shen, Jonathan B. Grimm, Natalie Falco, Bill Z. Jia, David Baker, Luke D. Lavis & Adam E. CohenÂ
doi : 10.1038/s41587-022-01524-7
Recording transcriptional histories of a cell would enable deeper understanding of cellular developmental trajectories and responses to external perturbations. Here we describe an engineered protein fiber that incorporates diverse fluorescent marks during its growth to store a ticker tape-like history.
Recording of cellular physiological histories along optically readable self-assembling protein chains
Changyang Linghu, Bobae An, Monika Shpokayte, Orhan T. Celiker, Nava Shmoel, Ruihan Zhang, Chi Zhang, Demian Park, Won Min Park, Steve Ramirez & Edward S. BoydenÂ
doi : 10.1038/s41587-022-01586-7
Observing cellular physiological histories is key to understanding normal and disease-related processes. Here we describe expression recording islands�a fully genetically encoded approach that enables both continual digital recording of biological information within cells and subsequent high-throughput readout in fixed cells.
Wireless, closed-loop, smart bandage with integrated sensors and stimulators for advanced wound care and accelerated healing
Yuanwen Jiang, Artem A. Trotsyuk, Simiao Niu, Dominic Henn, Kellen Chen, Chien-Chung Shih, Madelyn R. Larson, Alana M. Mermin-Bunnell, Smiti Mittal, Jian-Cheng Lai, Aref Saberi, Ethan Beard, Serena Jing, Donglai Zhong, Sydney R. Steele, Kefan Sun, Tanish Jain, Eric Zhao, Christopher R. Neimeth, Willian G. Viana, Jing Tang, Dharshan Sivaraj, Jagannath Padmanabhan, Melanie Rodrigues, David P. Perrault, Arhana Chattopadhyay, Zeshaan N. Maan, Melissa C. Leeolou, Clark A. Bonham, Sun Hyung Kwon, Hudson C. Kussie, Katharina S. Fischer, Gurupranav Gurusankar, Kui Liang, Kailiang Zhang, Ronjon Nag, Michael P. Snyder, Michael Januszyk, Geoffrey C. Gurtner & Zhenan BaoÂ
doi : 10.1038/s41587-022-01528-3
‘Smart’ bandages based on multimodal wearable devices could enable real-time physiological monitoring and active intervention to promote healing of chronic wounds. However, there has been limited development in incorporation of both sensors and stimulators for the current smart bandage technologies.
Re-engineering the adenine deaminase TadA-8e for efficient and specific CRISPR-based cytosine base editing
Liang Chen, Biyun Zhu, Gaomeng Ru, Haowei Meng, Yongchang Yan, Mengjia Hong, Dan Zhang, Changming Luan, Shun Zhang, Hao Wu, Hongyi Gao, Sijia Bai, Changqing Li, Ruoyi Ding, Niannian Xue, Zhixin Lei, Yuting Chen, Yuting Guan, Stefan Siwko, Yiyun Cheng, Gaojie Song, Liren Wang, Chengqi Yi, Mingyao Liu & Dali LiÂ
doi : 10.1038/s41587-022-01532-7
Cytosine base editors (CBEs) efficiently generate precise C·G-to-T·A base conversions, but the activation-induced cytidine deaminase/apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (AID/APOBEC) protein family deaminase component induces considerable off-target effects and indels. To explore unnatural cytosine deaminases, we repurpose the adenine deaminase TadA-8e for cytosine conversion.
Evolution of an adenine base editor into a small, efficient cytosine base editor with low off-target activity
Monica E. Neugebauer, Alvin Hsu, Mandana Arbab, Nicholas A. Krasnow, Amber N. McElroy, Smriti Pandey, Jordan L. Doman, Tony P. Huang, Aditya Raguram, Samagya Banskota, Gregory A. Newby, Jakub Tolar, Mark J. Osborn & David R. LiuÂ
doi : 10.1038/s41587-022-01533-6
Cytosine base editors (CBEs) are larger and can suffer from higher off-target activity or lower on-target editing efficiency than current adenine base editors (ABEs). To develop a CBE that retains the small size, low off-target activity and high on-target activity of current ABEs, we evolved the highly active deoxyadenosine deaminase TadA-8e to perform cytidine deamination using phage-assisted continuous evolution.
Improved cytosine base editors generated from TadA variants
Dieter K. Lam, Patricia R. Feliciano, Amena Arif, Tanggis Bohnuud, Thomas P. Fernandez, Jason M. Gehrke, Phil Grayson, Kin D. Lee, Manuel A. Ortega, Courtney Sawyer, Noah D. Schwaegerle, Leila Peraro, Lauren Young, Seung-Joo Lee, Giuseppe Ciaramella & Nicole M. GaudelliÂ
doi : 10.1038/s41587-022-01611-9
Cytosine base editors (CBEs) enable programmable genomic C·G-to-T·A transition mutations and typically comprise a modified CRISPR–Cas enzyme, a naturally occurring cytidine deaminase, and an inhibitor of uracil repair. Previous studies have shown that CBEs utilizing naturally occurring cytidine deaminases may cause unguided, genome-wide cytosine deamination.
Programmable eukaryotic protein synthesis with RNA sensors by harnessing ADAR
Kaiyi Jiang, Jeremy Koob, Xi Dawn Chen, Rohan N. Krajeski, Yifan Zhang, Verena Volf, Wenyuan Zhou, Samantha R. Sgrizzi, Lukas Villiger, Jonathan S. Gootenberg, Fei Chen & Omar O. AbudayyehÂ
doi : 10.1038/s41587-022-01534-5
Programmable approaches to sense and respond to the presence of specific RNAs in biological systems have broad applications in research, diagnostics, and therapeutics. Here we engineer a programmable RNA-sensing technology, reprogrammable ADAR sensors (RADARS), which harnesses RNA editing by adenosine deaminases acting on RNA (ADAR) to gate translation of a cargo protein by the presence of endogenous RNA transcripts.
Multifactorial profiling of epigenetic landscapes at single-cell resolution using MulTI-Tag
Michael P. Meers, Geneva Llagas, Derek H. Janssens, Christine A. Codomo & Steven HenikoffÂ
doi : 10.1038/s41587-022-01522-9
Chromatin profiling at locus resolution uncovers gene regulatory features that define cell types and developmental trajectories, but it remains challenging to map and compare different chromatin-associated proteins in the same sample. Here we describe Multiple Target Identification by Tagmentation (MulTI-Tag), an antibody barcoding approach for profiling multiple chromatin features simultaneously in single cells.
Protection of cell therapeutics from antibody-mediated killing by CD64 overexpression
Alessia Gravina, Grigol Tediashvili, Raja Rajalingam, Zoe Quandt, Chad Deisenroth, Sonja Schrepfer & Tobias DeuseÂ
doi : 10.1038/s41587-022-01540-7
Allogeneic cell therapeutics for cancer therapy or regenerative medicine are susceptible to antibody-mediated killing, which diminishes their efficacy. Here we report a strategy to protect cells from antibody-mediated killing that relies on engineered overexpression of the IgG receptor CD64. We
A single-center assessment of mental health and well-being in a biomedical sciences graduate program
Sarah K. Jachim, Bradley S. Bowles, Anjali J. Panicker, Iris Yousaf, Alyssa D. Brown, Alexander J. Zoroufy, Kasey R. Boehmer, Cynthia M. Stonnington, Tyler F. Vadeboncoeur, J. Luis Lujan, Shawna L. Ehlers & Autumn J. SchulzeÂ
