Nature Biotechnology 36, 205 (2018). doi:10.1038/nbt.4107

A new venture from Amazon, JP Morgans and Berkshire Hathaway has US healthcare in its crosshairs. It may also offer opportunities for innovators in health IT and digital medicine.

Author: Ken Garber

T cell receptor (TCR) gene therapy can target the immune system to solid tumors in ways CAR-T cells can't match, but the field is still looking for a clear success. Ken Garber reports.

Authors: Sadhana Chitale, Colm Lawler & Scott Macfarlane

What you need to know about the paperwork your institution requires when disclosing and commercializing your research.

Author: Vicki Seyfert-Margolis

Why digitally powered real-world evidence is the fix needed for our broken clinical trials system.

Author: Ennio Tasciotti

Tumor infarction is achieved through targeted delivery of thrombin by DNA nanorobots.

Author: Reinhard Heckel

New research sets a world record in the volume of data stored in and retrieved from DNA.

Authors: Hui Kwon Kim, Seonwoo Min, Myungjae Song, Soobin Jung, Jae Woo Choi, Younggwang Kim, Sangeun Lee, Sungroh Yoon & Hyongbum (Henry) Kim

Authors: Lee Organick, Siena Dumas Ang, Yuan-Jyue Chen, Randolph Lopez, Sergey Yekhanin, Konstantin Makarychev, Miklos Z Racz, Govinda Kamath, Parikshit Gopalan, Bichlien Nguyen, Christopher N Takahashi, Sharon Newman, Hsing-Yeh Parker, Cyrus Rashtchian, Kendall Stewart, Gagan Gupta, Robert Carlson, John Mulligan, Douglas Carmean, Georg Seelig, Luis Ceze & Karin Strauss

Authors: Ajaya K Biswal, Melani A Atmodjo, Mi Li, Holly L Baxter, Chang Geun Yoo, Yunqiao Pu, Yi-Ching Lee, Mitra Mazarei, Ian M Black, Ji-Yi Zhang, Hema Ramanna, Adam L Bray, Zachary R King, Peter R LaFayette, Sivakumar Pattathil, Bryon S Donohoe, Sushree S Mohanty, David Ryno, Kelsey Yee, Olivia A Thompson, Miguel Rodriguez, Alexandru Dumitrache, Jace Natzke, Kim Winkeler, Cassandra Collins, Xiaohan Yang, Li Tan, Robert W Sykes, Erica L Gjersing, Angela Ziebell, Geoffrey B Turner, Stephen R Decker, Michael G Hahn, Brian H Davison, Michael K Udvardi, Jonathan R Mielenz, Mark F Davis, Richard S Nelson, Wayne A Parrott, Arthur J Ragauskas, C Neal Stewart & Debra Mohnen

Authors: Suping Li, Qiao Jiang, Shaoli Liu, Yinlong Zhang, Yanhua Tian, Chen Song, Jing Wang, Yiguo Zou, Gregory J Anderson, Jing-Yan Han, Yung Chang, Yan Liu, Chen Zhang, Liang Chen, Guangbiao Zhou, Guangjun Nie, Hao Yan, Baoquan Ding & Yuliang Zhao

Nanoscale robots have potential as intelligent drug delivery systems that respond to molecular triggers. Using DNA origami we constructed an autonomous DNA robot programmed to transport payloads and present them specifically in tumors. Our nanorobot is functionalized on the outside with a DNA aptamer that binds nucleolin, a protein specifically expressed on tumor-associated endothelial cells, and the blood coagulation protease thrombin within its inner cavity. The nucleolin-targeting aptamer serves both as a targeting domain and as a molecular trigger for the mechanical opening of the DNA nanorobot. The thrombin inside is thus exposed and activates coagulation at the tumor site. Using tumor-bearing mouse models, we demonstrate that intravenously injected DNA nanorobots deliver thrombin specifically to tumor-associated blood vessels and induce intravascular thrombosis, resulting in tumor necrosis and inhibition of tumor growth. The nanorobot proved safe and immunologically inert in mice and Bama miniature pigs. Our data show that DNA nanorobots represent a promising strategy for precise drug delivery in cancer therapy.

Authors: Antonio Casini, Michele Olivieri, Gianluca Petris, Claudia Montagna, Giordano Reginato, Giulia Maule, Francesca Lorenzin, Davide Prandi, Alessandro Romanel, Francesca Demichelis, Alberto Inga & Anna Cereseto

Despite the utility of CRISPR–Cas9 nucleases for genome editing, the potential for off-target activity limits their application, especially for therapeutic purposes. We developed a yeast-based assay to identify optimized Streptococcus pyogenes Cas9 (SpCas9) variants that enables simultaneous evaluation of on- and off-target activity. We screened a library of SpCas9 variants carrying random mutations in the REC3 domain and identified mutations that increased editing accuracy while maintaining editing efficiency. We combined four beneficial mutations to generate evoCas9, a variant that has fidelity exceeding both wild-type (79-fold improvement) and rationally designed Cas9 variants (fourfold average improvement), while maintaining near wild-type on-target editing efficiency (90% median residual activity). Evaluating evoCas9 on endogenous genomic loci, we demonstrated a substantially improved specificity and observed no off-target sites for four of the eight single guide RNAs (sgRNAs) tested. Finally, we showed that following long-term expression (40 d), evoCas9 strongly limited the nonspecific cleavage of a difficult-to-discriminate off-target site and fully abrogated the cleavage of two additional off-target sites.

Authors: Elizabeth Brunk, Swagatika Sahoo, Daniel C Zielinski, Ali Altunkaya, Andreas Dräger, Nathan Mih, Francesco Gatto, Avlant Nilsson, German Andres Preciat Gonzalez, Maike Kathrin Aurich, Andreas Prlić, Anand Sastry, Anna D Danielsdottir, Almut Heinken, Alberto Noronha, Peter W Rose, Stephen K Burley, Ronan M T Fleming, Jens Nielsen, Ines Thiele & Bernhard O Palsson

Authors: Teresa M Evans, Lindsay Bira, Jazmin Beltran Gastelum, L Todd Weiss & Nathan L Vanderford

With mental illness a growing concern within graduate education, data from a new survey should prompt both academia and policy makers to consider intervention strategies.