Table of contents


In This Issue

In this issue ppvii - viii




Enlightened engineering p849


Optogenetics—until now primarily a tool for asking questions in basic research—is starting to spur efforts oriented toward biomedical applications.

Seattle Genetics rare cancer drug sails through accelerated approval pp851 - 852

Laura DeFrancesco


HIV drugs made in tobacco p852

Jeffrey L Fox


Engineered T-cell therapy shows efficacy in blood cancer pp853 - 855

Simon Frantz


9,000 tumors for stratified medicine p854

Susan Aldridge


Chinese inventors catch up p854

Nuala Moran


ATM cash for biotechs p856

Brian Orelli


Pertuzumab to bolster Roche/Genentech's breast cancer franchise? pp856 - 858

Cormac Sheridan


Gilead donates patents for generics p857

Simon Frantz


South Korea's stem cell approval p857

Heiko Yang


Data Page

Drug pipeline: Q311 p859

Wayne Peng



News Feature

Attacks on asthma pp860 - 863

Sarah Webb


The current standard of care for asthma leaves large numbers of sufferers at risk for severe exacerbations and even death. But emerging targeted therapies that may provide better treatment options also face obstacles. Sarah Webb reports.



Building a business

Headwinds into opportunity pp864 - 866

Prabhavathi Fernandes


Numerous challenges face any emerging company developing a biopharmaceutical. How you anticipate hurdles, plan for contingencies and communicate with stakeholders will play a big part in determining your success.


Opinion and Comment


A methodological framework to enhance the clinical success of cancer immunotherapy pp867 - 870

Axel Hoos, Cedrik M Britten, Christoph Huber & Jill O'Donnell-Tormey


Pharmacogenetics and the immunogenicity of protein therapeutics pp870 - 873

Chen Yanover, Nisha Jain, Glenn Pierce, Tom E Howard & Zuben E Sauna


Wanted: bioprospecting consultants pp873 - 875

Kazuo N Watanabe & Guat Hong Teh





Evergreening: a common practice to protect new drugs pp876 - 878

Kate S Gaudry


The common strategy of evergreening using patents and other exclusivity periods likely contributes to the total incentives that justify a pharmaceutical company's investment in a new drug.


News and Views

New fluorescent probes for super-resolution imaging pp880 - 881

Joshua C Vaughan & Xiaowei Zhuang


Fatigue-resistant, photoswitchable fluorescent proteins facilitate sub-diffraction-limit imaging of living cells with low light intensity.

See also: Research by Brakemann et al.

Tracking down the human myelinating cell pp881 - 883

Robert H Miller & Paul J Tesar


A new strategy for isolating oligodendrocyte progenitor cells from the human brain may advance the goal of therapeutic remyelination.

See also: Research by Sim et al.

RNA lights up pp883 - 884

John S Mattick & Michael B Clark


A new method to genetically tag RNA for fluorescence imaging in live cells simplifies imaging of cellular RNAs.


Research Highlights


Computational Biology


Extracting a cellular hierarchy from high-dimensional cytometry data with SPADE pp886 - 891

Peng Qiu, Erin F Simonds, Sean C Bendall, Kenneth D Gibbs Jr, Robert V Bruggner, Michael D Linderman, Karen Sachs, Garry P Nolan & Sylvia K Plevritis


New instruments can measure the presence of >30 molecular markers for massive numbers of single cells, but data analysis algorithms have lagged behind. Qiu et al. describe an approach called SPADE for recovering cellular hierarchies from mass or flow cytometry data.




Direct lineage conversions: unnatural but useful? pp892 - 907

Thomas Vierbuchen & Marius Wernig



Performance comparison of exome DNA sequencing technologies pp908 - 914

Michael J Clark, Rui Chen, Hugo Y K Lam, Konrad J Karczewski, Rong Chen, Ghia Euskirchen, Atul J Butte & Michael Snyder


Capturing and sequencing only the coding regions of the human genome leverages resources in the pursuit of rare disease-causing mutations. Clark et al. compare the performance of three leading exome-capture methods and their advantages over whole-genome sequencing.


Efficient de novo assembly of single-cell bacterial genomes from short-read data sets pp915 - 921

Hamidreza Chitsaz, Joyclyn L Yee-Greenbaum, Glenn Tesler, Mary-Jane Lombardo, Christopher L Dupont, Jonathan H Badger, Mark Novotny, Douglas B Rusch, Louise J Fraser, Niall A Gormley, Ole Schulz-Trieglaff, Geoffrey P Smith, Dirk J Evers, Pavel A Pevzner & Roger S Lasken


DNA can be amplified and sequenced from a single cell, but unevenness of the sequence coverage complicates efforts to assemble a high-quality genome. Chitsaz et al. devise an algorithm to address this problem and apply it to assemble a genome draft of an uncultured single-cell marine organism from one lane of Illumina sequence data.

Comparative genomic analysis of the thermophilic biomass-degrading fungi Myceliophthora thermophila and Thielavia terrestris pp922 - 927

Randy M Berka, Igor V Grigoriev, Robert Otillar, Asaf Salamov, Jane Grimwood, Ian Reid, Nadeeza Ishmael, Tricia John, Corinne Darmond, Marie-Claude Moisan, Bernard Henrissat, Pedro M Coutinho, Vincent Lombard, Donald O Natvig, Erika Lindquist, Jeremy Schmutz, Susan Lucas, Paul Harris, Justin Powlowski, Annie Bellemare, David Taylor, Gregory Butler, Ronald P de Vries, Iris E Allijn, Joost van den Brink, Sophia Ushinsky, Reginald Storms, Amy J Powell, Ian T Paulsen, Liam D H Elbourne, Scott E Baker, Jon Magnuson, Sylvie LaBoissiere, A John Clutterbuck, Diego Martinez, Mark Wogulis, Alfredo Lopez de Leon, Michael W Rey & Adrian Tsang


Thermostable enzymes are used for a range of industrial processes, including biofuel production. Berka et al. report the genome sequences of two thermophilic eukaryotic fungi with enzymes that operate at the elevated temperatures needed to digest biomass and prepare many biochemicals.

Tracking single hematopoietic stem cells in vivo using high-throughput sequencing in conjunction with viral genetic barcoding pp928 - 933

Rong Lu, Norma F Neff, Stephen R Quake & Irving L Weissman


Heterogeneity within populations of stem cells, cancer cells or other cell types of interest presents a formidable barrier to analysis. Lu et al. use viral barcoding and high-throughput sequencing to track the differentiation of single hematopoietic stem cells in vivo.

CD140a identifies a population of highly myelinogenic, migration-competent and efficiently engrafting human oligodendrocyte progenitor cells pp934 - 941

Fraser J Sim, Crystal R McClain, Steven J Schanz, Tricia L Protack, Martha S Windrem & Steven A Goldman


Oligodendrocyte progenitors capable of myelination in myelin-deficient mice have been isolated from human fetal brain cells, but at low purity. Sim et al. show that sorting based on PDGFRα expression yields a purer population of myelinogenic cells free of neuronal and committed astrocyte cells.

See also: News and Views by Miller & Tesar

A reversibly photoswitchable GFP-like protein with fluorescence excitation decoupled from switching pp942 - 947

Tanja Brakemann, Andre C Stiel, Gert Weber, Martin Andresen, Ilaria Testa, Tim Grotjohann, Marcel Leutenegger, Uwe Plessmann, Henning Urlaub, Christian Eggeling, Markus C Wahl, Stefan W Hell & Stefan Jakobs


Brakemann et al. present a reversibly photoswitchable fluorescent protein, called Dreiklang, that can be turned on and off at wavelengths distinct from those used for imaging. They show that the protein is advantageous for studying protein dynamics in living cells and for super-resolution imaging.

See also: News and Views by Vaughan & Zhuang


Careers and Recruitment

A global need for women's biotech leadership pp948 - 949

Laurel Smith-Doerr, Gintare Kemekliene, Rita Teutonico, Lene Lange, Lydia Villa-Komaroff, Line Matthiessen-Guyader & Fiona Murray


Increasing women's participation in leadership of biotech policy making, funding, research and implementation will strengthen the race to solve global problems.


People p950