Table of contents


In This Issue

In this issue ppvii - viii



Focus on Plant Technologies

Plant Technologies

Sixteen years after the commercialization of crops produced by traditional transgenic technology, a raft of new approaches are opening new opportunities in plant biotechnology. This focus issue of Nature Biotechnology highlights these technologies and their impact on plant breeding and their impact on regulatory oversight.



Focus on Plant Technologies

Agnostic about agriculture p197


Averting a global food crisis will require the deconstruction of several hurdles to the deployment of new strategies in plant breeding.

Another nail in the biosimilar coffin? p198


The US Food and Drug Administration (FDA) has raised the bar very high for those who seek to make a business out of biosimilars.

Companies in rapid pursuit of Btk immunokinase pp199 - 200

Cormac Sheridan


One patent for Europe p200

Gunjan Sinha


Cystic fibrosis drug Vertex's latest triumph pp201 - 202

Heidi Ledford


Diabetes once-weekly drug p201

Gunjan Sinha


Check a patent at WIPO p202

Michael Francisco


RNAi patent win p202

Jennifer Rohn


Hedgehog hopes lifted by approval... and stung by failure p203

Malorye Allison


NCATS launches p204

Jeffrey L Fox


BASF moves GM crop research to US p204

Lucas Laursen


HIV neutralizing antibodies reignite interest in vaccine pp204 - 205

Emily Waltz


Around the world in a month p205


Mission Therapeutics p206

Ken Garber


Synthetic lethality pioneers spin out an oncology company targeting DNA repair through interruption of ubiquitin pathways.

Data Page

Focus on Plant Technologies

Existing agbiotech traits continue global march p207

Andrew Marshall



Focus on Plant Technologies

Confronting the Gordian knot pp208 - 209

L Val Giddings, Ingo Potrykus, Klaus Ammann & Nina V Fedoroff


Galvanizing plant science in Europe will depend on an overhaul of the tangle of indefensible regulations themselves, not on the advent of new plant breeding technologies that may escape existing rules.

News Features

Focus on Plant Technologies

Agbiotech 2.0 pp211 - 214

Daniel Gruskin


As parts of the developing world embrace biotech, the focus is shifting from food production to fuels, industrial chemicals and even drugs. Daniel Grushkin investigates.

Focus on Plant Technologies

Tiptoeing around transgenics pp215 - 217

Emily Waltz


New techniques for manipulating plant genomes are yielding plants touted as nontransgenic. Will that relieve regulatory burden? Emily Waltz investigates.



Know before you go pp219 - 220

Mark Kessel




The Chromosome-Centric Human Proteome Project for cataloging proteins encoded in the genome pp221 - 223

Young-Ki Paik, Seul-Ki Jeong, Gilbert S Omenn, Mathias Uhlen, Samir Hanash, Sang Yun Cho, Hyoung-Joo Lee, Keun Na, Eun-Young Choi, Fangfei Yan, Fan Zhang, Yue Zhang, Michael Snyder, Yong Cheng, Rui Chen, György Marko-Varga, Eric W Deutsch, Hoguen Kim, Ja-Young Kwon, Ruedi Aebersold, Amos Bairoch, Allen D Taylor, Kwang Youl Kim, Eun-Young Lee, Denis Hochstrasser, Pierre Legrain & William S. Hancock


BLUEPRINT to decode the epigenetic signature written in blood pp224 - 226

David Adams, Lucia Altucci, Stylianos E Antonarakis, Juan Ballesteros, Stephan Beck, Adrian Bird, Christoph Bock, Bernhard Boehm, Elias Campo, Andrea Caricasole, Fredrik Dahl, Emmanouil T Dermitzakis, Tariq Enver, Manel Esteller, Xavier Estivill, Anne Ferguson-Smith, Jude Fitzgibbon, Paul Flicek, Claudia Giehl, Thomas Graf, Frank Grosveld, Roderic Guigo, Ivo Gut, Kristian Helin, Jonas Jarvius, Ralf Küppers, Hans Lehrach, Thomas Lengauer, Åke Lernmark, David Leslie, Markus Loeffler, Elizabeth Macintyre, Antonello Mai, Joost HA Martens, Saverio Minucci, Willem H Ouwehand, Pier Giuseppe Pelicci, Hèléne Pendeville, Bo Porse, Vardhman Rakyan, Wolf Reik, Martin Schrappe, Dirk Schübeler, Martin Seifert, Reiner Siebert, David Simmons, Nicole Soranzo, Salvatore Spicuglia, Michael Stratton, Hendrik G Stunnenberg, Amos Tanay, David Torrents, Alfonso Valencia, Edo Vellenga, Martin Vingron, Jörn Walter & Spike Willcocks


Detecting and annotating genetic variations using the HugeSeq pipeline pp226 - 229

Hugo Y K Lam, Cuiping Pan, Michael J Clark, Phil Lacroute, Rui Chen, Rajini Haraksingh, Maeve O'Huallachain, Mark B Gerstein, Jeffrey M Kidd, Carlos D Bustamante & Michael Snyder


Update on the first cloned goats pp229 - 230

Stephen Blash, Michael Schofield, Yann Echelard & William Gavin




Focus on Plant Technologies

Deployment of new biotechnologies in plant breeding pp231 - 239

Maria Lusser, Claudia Parisi, Damien Plan & Emilio Rodríguez-Cerezo


The first crops obtained through new plant breeding techniques are close to commercialization. Regulatory issues will determine the adoption of the techniques by breeders.


Debunking the myth that whole-genome sequencing infringes thousands of gene patents pp240 - 244

Christopher M Holman


The fear that human gene patents pose a threat to whole-genome sequencing is based largely on widely held misconceptions.

Recent patent applications in single-molecule technologies p245

Julien Muzard



News and Views

A closer look at RNA editing pp246 - 247

Lior Pachter


An improved method for analyzing deep RNA sequencing data provides a comprehensive view of RNA editing sites.

See also: Computational Biology by Peng et al.

Tracing the genesis of human embryonic stem cells pp247 - 249

Ariel Pribluda & Jacob H Hanna


When human blastocysts are cultured in vitro to derive embryonic stem cells, they undergo profound molecular changes that alter their identity.

See also: Research by O'Leary et al.

Profiling PARP inhibitors pp249 - 250

Philip Jones


A comprehensive study of ligand binding to the human PARP family of proteins reveals the molecular basis of inhibitor selectivity and promiscuity.

See also: Research by Wahlberg et al.


Research Highlights


Computational Biology


Comprehensive analysis of RNA-Seq data reveals extensive RNA editing in a human transcriptome pp253 - 260

Zhiyu Peng, Yanbing Cheng, Bertrand Chin-Ming Tan, Lin Kang, Zhijian Tian, Yuankun Zhu, Wenwei Zhang, Yu Liang, Xueda Hu, Xuemei Tan, Jing Guo, Zirui Dong, Yan Liang, Li Bao & Jun Wang


Sites where RNA editing occurs can be found using RNA-Seq, but false positives confound the data analysis. Peng et al. describe algorithms for accurately calling editing events, and apply them to identify ~22,600 events, mostly Aright arrowG changes, in a human transcriptome.

See also: News and Views by Pachter



Brief Communications

Functional beta-cell maturation is marked by an increased glucose threshold and by expression of urocortin 3 pp261 - 264

Barak Blum, Sinis breveša Hrvatin, Christian Schuetz, Claire Bonal, Alireza Rezania & Douglas A Melton


Cultured human pluripotent stem cells can be differentiated to immature pancreatic beta cells, but no one has yet succeeded in maturing these cells in vitro. Blum et al. define markers of beta-cell maturation that can be used to screen conditions for generating fully functional beta cells.


Massively parallel functional dissection of mammalian enhancers in vivo pp265 - 270

Rupali P Patwardhan, Joseph B Hiatt, Daniela M Witten, Mee J Kim, Robin P Smith, Dalit May, Choli Lee, Jennifer M Andrie, Su-In Lee, Gregory M Cooper, Nadav Ahituv, Len A Pennacchio & Jay Shendure


Two groups describe approaches for synthesizing and assaying the function of thousands of variants of mammalian DNA regulatory elements. Melnikov et al. use their results to engineer short optimized regulatory elements in human cells, whereas Patwardhan et al. study enhancers hundreds of bases long in mice.

Systematic dissection and optimization of inducible enhancers in human cells using a massively parallel reporter assay pp271 - 277

Alexandre Melnikov, Anand Murugan, Xiaolan Zhang, Tiberiu Tesileanu, Li Wang, Peter Rogov, Soheil Feizi, Andreas Gnirke, Curtis G Callan Jr, Justin B Kinney, Manolis Kellis, Eric S Lander & Tarjei S Mikkelsen


An improved understanding of enhancers in mammalian genomes could facilitate the design of new regulatory elements. Melnikov et al. synthesize thousands of ~90 nt enhancer variants, assay their activity in human cells and use the data to rationally optimize synthetic enhancers.


Tracking the progression of the human inner cell mass during embryonic stem cell derivation pp278 - 282

Thomas O'Leary, Björn Heindryckx, Sylvie Lierman, David van Bruggen, Jelle J Goeman, Mado Vandewoestyne, Dieter Deforce, Susana M Chuva de Sousa Lopes & Petra De Sutter


The events that lead from plated human blastocysts to embryonic stem cells are poorly understood. Close analysis reveals a transient intermediate state with a distinct molecular profile.

See also: News and Views by Pribluda & Hanna


Family-wide chemical profiling and structural analysis of PARP and tankyrase inhibitors pp283 - 288

Elisabet Wahlberg, Tobias Karlberg, Ekaterina Kouznetsova, Natalia Markova, Antonio Macchiarulo, Ann-Gerd Thorsell, Ewa Pol, Åsa Frostell, Torun Ekblad, Delal Öncü, Björn Kull, Graeme Michael Robertson, Roberto Pellicciari, Herwig Schüler & Johan Weigelt


PARP inhibitors have recently entered phase 3 clinical trials as cancer therapeutics, but the specificity of many of these compounds is unknown. Wahlberg et al. used biochemical approaches to show that most PARP inhibitors target multiple PARP family members.

See also: News and Views by Jones


Careers and Recruitment

Pay increases for executives at private life sciences companies hit a 12-year low pp289 - 291

Bruce Rychlik


In 2011, year-over-year executive cash compensation increased just 1.6%, well below the historical 5% annual rise, according to a nationwide survey.


People p292