Articles in 2010

  • Article |

    TALEs (transcription activator-like effectors) are transcription factors from the plant pathogen Xanthomonas that can be readily engineered to bind new DNA sequences of interest. Miller et al. use a truncated TALE linked to a nuclease domain to edit and regulate endogenous genes in human cells.

    • Jeffrey C Miller
    • , Siyuan Tan
    • , Guijuan Qiao
    • , Kyle A Barlow
    • , Jianbin Wang
    • , Danny F Xia
    • , Xiangdong Meng
    • , David E Paschon
    • , Elo Leung
    • , Sarah J Hinkley
    • , Gladys P Dulay
    • , Kevin L Hua
    • , Irina Ankoudinova
    • , Gregory J Cost
    • , Fyodor D Urnov
    • , H Steve Zhang
    • , Michael C Holmes
    • , Lei Zhang
    • , Philip D Gregory
    •  & Edward J Rebar
  • Letter |

    Sequencing a human genome using next-generation methods does not distinguish between the two copies of each chromosome. Kitzman et al. determine a haplotype-resolved genome sequence by efficiently constructing and sequencing long-insert clones that cover the diploid genome with a low likelihood of overlap.

    • Jacob O Kitzman
    • , Alexandra P MacKenzie
    • , Andrew Adey
    • , Joseph B Hiatt
    • , Rupali P Patwardhan
    • , Peter H Sudmant
    • , Sarah B Ng
    • , Can Alkan
    • , Ruolan Qiu
    • , Evan E Eichler
    •  & Jay Shendure
  • Article |

    The two copies of each chromosome in a diploid organism may contain different patterns of genetic variants. Fan et al. describe a microfluidic device capable of isolating each of the sister chromatids from single cells, allowing whole-genome haplotyping by sequencing and arrays.

    • H Christina Fan
    • , Jianbin Wang
    • , Anastasia Potanina
    •  & Stephen R Quake
  • Letter |

    Song et al. present the first method for global analysis of 5-hydroxymethylcytosine, a recently identified epigenetic modification in mammalian cells. They use a bacteriophage-derived enzyme to tag the hydroxymethyl group with an azide-modified glucose residue that can be used for affinity purification and sequencing of modified genomic DNA fragments.

    • Chun-Xiao Song
    • , Keith E Szulwach
    • , Ye Fu
    • , Qing Dai
    • , Chengqi Yi
    • , Xuekun Li
    • , Yujing Li
    • , Chih-Hsin Chen
    • , Wen Zhang
    • , Xing Jian
    • , Jing Wang
    • , Li Zhang
    • , Timothy J Looney
    • , Baichen Zhang
    • , Lucy A Godley
    • , Leslie M Hicks
    • , Bruce T Lahn
    • , Peng Jin
    •  & Chuan He
  • Letter |

    If transgenes are to be introduced into the genome for cell therapies, the integration events should permit high transgene expression without altering the expression of endogenous genes. Papapetrou et al. propose five criteria to define such 'safe harbors' in the human genome and demonstrate high A-globin expression from a safe-harbor site in erythroid-lineage cells derived from induced pluripotent stem (iPS) cells.

    • Eirini P Papapetrou
    • , Gabsang Lee
    • , Nirav Malani
    • , Manu Setty
    • , Isabelle Riviere
    • , Laxmi M S Tirunagari
    • , Kyuichi Kadota
    • , Shoshannah L Roth
    • , Patricia Giardina
    • , Agnes Viale
    • , Christina Leslie
    • , Frederic D Bushman
    • , Lorenz Studer
    •  & Michel Sadelain
  • Letter |

    Cui et al. generate transgenic rats and mice bearing targeted genomic integrations by enhancing the rate of homologous recombination in single-cell embryos with zinc-finger nucleases. The approach avoids the time-consuming backcrossing involved in generating mutant mice with ES cells and should be applicable to species for which ES cells have not been isolated.

    • Xiaoxia Cui
    • , Diana Ji
    • , Daniel A Fisher
    • , Yumei Wu
    • , David M Briner
    •  & Edward J Weinstein
  • Commentary |

    The antiquated legal standard that natural laws and products are not eligible for patent protection is ill-suited for gene and diagnostics patents. Here, I propose a new, technology-agnostic framework for determining patent eligibility that is tailored to the meet the US Constitutional objective of promoting innovation.

    • Kenneth G Chahine
  • Correspondence |

    • Mathias Uhlen
    • , Per Oksvold
    • , Linn Fagerberg
    • , Emma Lundberg
    • , Kalle Jonasson
    • , Mattias Forsberg
    • , Martin Zwahlen
    • , Caroline Kampf
    • , Kenneth Wester
    • , Sophia Hober
    • , Henrik Wernerus
    • , Lisa Björling
    •  & Fredrik Ponten
  • Careers and Recruitment |

  • Editorial |

    The Obama administration's $1 billion tax program at the very least signals a continued commitment to innovative biotech. The same cannot be said of plans afoot by the French government.

  • News & Views |

    Two approaches for selecting oligonucleotides from complex mixtures improve the fidelity and scalability of DNA synthesis.

    • Mikkel Algire
    • , Radha Krishnakumar
    •  & Chuck Merryman
  • Patents |

    The development of generic therapeutic nanoparticles faces a combination of scientific, patent and regulatory challenges.

    • Paul Burgess
    • , Peter Barton Hutt
    • , Omid C Farokhzad
    • , Robert Langer
    • , Scott Minick
    •  & Stephen Zale
  • Erratum |

    • Halla Thorsteinsdóttir
    • , Christina C Melon
    • , Monali Ray
    • , Sharon Chakkalackal
    • , Michelle Li
    • , Jan E Cooper
    • , Jennifer Chadder
    • , Tirso W Saenz
    • , Maria Carlota de Souza Paula
    • , Wen Ke
    • , Lexuan Li
    • , Magdy A Madkour
    • , Sahar Aly
    • , Nefertiti El-Nikhely
    • , Sachin Chaturvedi
    • , Victor Konde
    • , Abdallah S Daar
    •  & Peter A Singer
  • News Feature |

    Only one drug targeting the proteasome protein degradation pathway has been approved, but several second-generation inhibitors are making progress in trials. Jim Kling reports.

    • Jim Kling
  • Corrigendum |

    • Dong-Uk Kim
    • , Jacqueline Hayles
    • , Dongsup Kim
    • , Valerie Wood
    • , Han-Oh Park
    • , Misun Won
    • , Hyang-Sook Yoo
    • , Trevor Duhig
    • , Miyoung Nam
    • , Georgia Palmer
    • , Sangjo Han
    • , Linda Jeffery
    • , Seung-Tae Baek
    • , Hyemi Lee
    • , Young Sam Shim
    • , Minho Lee
    • , Lila Kim
    • , Kyung-Sun Heo
    • , Eun Joo Noh
    • , Ah-Reum Lee
    • , Young-Joo Jang
    • , Kyung-Sook Chung
    • , Shin-Jung Choi
    • , Jo-Young Park
    • , Youngwoo Park
    • , Hwan Mook Kim
    • , Song-Kyu Park
    • , Hae-Joon Park
    • , Eun-Jung Kang
    • , Hyong Bai Kim
    • , Hyun-Sam Kang
    • , Hee-Moon Park
    • , Kyunghoon Kim
    • , Kiwon Song
    • , Kyung Bin Song
    • , Paul Nurse
    •  & Kwang-Lae Hoe
  • Careers and Recruitment |

    China is presenting the pharmaceutical world with unprecedented opportunity. Here is what is happening there and how you can be a part of it.

    • Connie Johnson Hambley
  • News & Views |

    An imaging study begins to define the parameters that control the biodistribution of nanoparticles after pulmonary delivery.

    • Wolfgang G Kreyling
    • , Stephanie Hirn
    •  & Carsten Schleh
  • Correspondence |

    • Robert Cook-Deegan
    • , Subhashini Chandrasekharan
    • , Misha Angrist
    • , Bhaven Sampat
    • , E Richard Gold
    • , Julia Carbone
    •  & Lori Knowles
  • News & Views |

    The sterile insect technique offers an alternative to the refuge strategy for managing resistance to Bt toxins.

    • Kongming Wu
  • Feature |

    First-generation epigenetic drugs have proven clinically useful in several hematological cancers. But newer enzyme inhibitors in the pipeline aim to be more selective and promise to broaden the portfolio of therapeutic uses.

    • George S Mack
  • News Feature |

    The list of drug companies forced into several hundred million dollar settlements for making fraudulent product claims continues to lengthen. And the signs are that the US government will continue to ramp up its efforts, using new theories of liability and handing out even stiffer penalties. Mark Ratner investigates.

    • Mark Ratner
  • Commentary |

    Action needs to be taken to prevent anti-biotech activists from co-opting environmental law to derail the planting of transgenic crops that have already received regulatory approval.

    • Gregory Conko
    •  & Henry I Miller
  • Corrigendum |

    • Emek Demir
    • , Michael P Cary
    • , Suzanne Paley
    • , Ken Fukuda
    • , Christian Lemer
    • , Imre Vastrik
    • , Guanming Wu
    • , Peter D'Eustachio
    • , Carl Schaefer
    • , Joanne Luciano
    • , Frank Schacherer
    • , Irma Martinez-Flores
    • , Zhenjun Hu
    • , Veronica Jimenez-Jacinto
    • , Geeta Joshi-Tope
    • , Kumaran Kandasamy
    • , Alejandra C Lopez-Fuentes
    • , Huaiyu Mi
    • , Elgar Pichler
    • , Igor Rodchenkov
    • , Andrea Splendiani
    • , Sasha Tkachev
    • , Jeremy Zucker
    • , Gopal Gopinath
    • , Harsha Rajasimha
    • , Ranjani Ramakrishnan
    • , Imran Shah
    • , Mustafa Syed
    • , Nadia Anwar
    • , Özgün Babur
    • , Michael Blinov
    • , Erik Brauner
    • , Dan Corwin
    • , Sylva Donaldson
    • , Frank Gibbons
    • , Robert Goldberg
    • , Peter Hornbeck
    • , Augustin Luna
    • , Peter Murray-Rust
    • , Eric Neumann
    • , Oliver Reubenacker
    • , Matthias Samwald
    • , Martijn van Iersel
    • , Sarala Wimalaratne
    • , Keith Allen
    • , Burk Braun
    • , Michelle Whirl-Carrillo
    • , Kei-Hoi Cheung
    • , Kam Dahlquist
    • , Andrew Finney
    • , Marc Gillespie
    • , Elizabeth Glass
    • , Li Gong
    • , Robin Haw
    • , Michael Honig
    • , Olivier Hubaut
    • , David Kane
    • , Shiva Krupa
    • , Martina Kutmon
    • , Julie Leonard
    • , Debbie Marks
    • , David Merberg
    • , Victoria Petri
    • , Alex Pico
    • , Dean Ravenscroft
    • , Liya Ren
    • , Nigam Shah
    • , Margot Sunshine
    • , Rebecca Tang
    • , Ryan Whaley
    • , Stan Letovksy
    • , Kenneth H Buetow
    • , Andrey Rzhetsky
    • , Vincent Schachter
    • , Bruno S Sobral
    • , Ugur Dogrusoz
    • , Shannon McWeeney
    • , Mirit Aladjem
    • , Ewan Birney
    • , Julio Collado-Vides
    • , Susumu Goto
    • , Michael Hucka
    • , Nicolas Le Novère
    • , Natalia Maltsev
    • , Akhilesh Pandey
    • , Paul Thomas
    • , Edgar Wingender
    • , Peter D Karp
    • , Chris Sander
    •  & Gary D Bader
  • Letter |

    The use of shRNA in vivo to investigate genes involved in proliferation and survival is confounded by the competitive advantage of cells with insufficient shRNA expression. Zuber et al. address this issue with a system that combines Tet-regulated shRNA expression, two fluorescent reporters and robust transactivator production.

    • Johannes Zuber
    • , Katherine McJunkin
    • , Christof Fellmann
    • , Lukas E Dow
    • , Meredith J Taylor
    • , Gregory J Hannon
    •  & Scott W Lowe
  • Letter |

    DNA molecules that are read by a next-generation sequencer have been discarded after the sequencing reaction, until now. By retrieving oil-emulsified beads encapsulating DNA with a known sequence, Matzas et al. obtain high-quality input material for DNA synthesis.

    • Mark Matzas
    • , Peer F Stähler
    • , Nathalie Kefer
    • , Nicole Siebelt
    • , Valesca Boisguérin
    • , Jack T Leonard
    • , Andreas Keller
    • , Cord F Stähler
    • , Pamela Häberle
    • , Baback Gharizadeh
    • , Farbod Babrzadeh
    •  & George M Church
  • Letter |

    Long DNA molecules, such as those encoding genes, can be assembled from short oligonucleotides created on a microarray. Kosuri et al. improve the fidelity and scalability of this process, enabling synthesis of 40 antibody fragments having repetitive regions and other challenging sequence features.

    • Sriram Kosuri
    • , Nikolai Eroshenko
    • , Emily M LeProust
    • , Michael Super
    • , Jeffrey Way
    • , Jin Billy Li
    •  & George M Church
  • Analysis |

    The metabolism of tissues often involves interactions between several types of cell. Lewis et al. model metabolism within and between neurons in the human brain, gaining insight into energy metabolism and Alzheimer's disease.

    • Nathan E Lewis
    • , Gunnar Schramm
    • , Aarash Bordbar
    • , Jan Schellenberger
    • , Michael P Andersen
    • , Jeffrey K Cheng
    • , Nilam Patel
    • , Alex Yee
    • , Randall A Lewis
    • , Roland Eils
    • , Rainer König
    •  & Bernhard Ø Palsson
  • Brief Communication |

    Minicircle DNA vectors are superior to plasmids for long-term transgene expression but are not in widespread use because of a laborious production process. Kay et al. present an improved protocol for generating minicircles that makes them a viable alternative to plasmids for gene transfer studies.

    • Mark A Kay
    • , Cheng-Yi He
    •  & Zhi-Ying Chen
  • Letter |

    Nanoparticles are under study for pulmonary drug delivery and are continually in contact with the lungs through air pollution. Choi et al. study the effects of size, charge and chemical composition on the behavior of nanoparticles in the rat lung.

    • Hak Soo Choi
    • , Yoshitomo Ashitate
    • , Jeong Heon Lee
    • , Soon Hee Kim
    • , Aya Matsui
    • , Numpon Insin
    • , Moungi G Bawendi
    • , Manuela Semmler-Behnke
    • , John V Frangioni
    •  & Akira Tsuda
  • Letter |

    Adaptation of insect pests to tolerate Bacillus thuringiensis (Bt) insecticidal proteins threatens to reduce the efficacy of Bt crops. Evidence from an extensive four-year field trial indicates that the release of sterile pink bollworm moths suppresses the emergence of resistance to transgenic Bt cotton, while helping to eradicate the pest.

    • Bruce E Tabashnik
    • , Mark S Sisterson
    • , Peter C Ellsworth
    • , Timothy J Dennehy
    • , Larry Antilla
    • , Leighton Liesner
    • , Mike Whitlow
    • , Robert T Staten
    • , Jeffrey A Fabrick
    • , Gopalan C Unnithan
    • , Alex J Yelich
    • , Christa Ellers-Kirk
    • , Virginia S Harpold
    • , Xianchun Li
    •  & Yves Carrière
  • Editorial |

    Claims of conflicts of interest concerning authorship of a scientific paper highlight the difficulties facing regulators participating in collaborations with industry.