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More than 75% of in its editorial review process. · 2018. 2. 13. · Coverage and Reimbursement of Advanced Diagnostics DNA Forensics Clinical NGSAssays Hospital Laboratory Design

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    PNASwww.pnas.org

    Submissions are accepted fromresearchers all over the world.Authors do not need to have a connection toan NAS member to publish in PNAS.

    PNAS is committed to transparencyin its editorial review process.

    FAQs for authors explaining the review process are

    available at www.pnas.org/site/authors/authorfaq.xhtml.

    All articles are evaluated solelyon their scientific merit by peers—

    not by staff editors. Accepted papers must be of exceptional

    scientific importance and intelligible to a broad scientific audience.

    More than 75% ofpublished papersare submitteddirectly to PNAS—not contributed by NAS members.

    How it works…PNAS Submission & Editorial Review

    1 Editorial Board Member—from one of the 31 NAS disciplines.

    A full list of Editorial Board members and their disciplines is

    available at www.pnas.org/misc/masthead.xhtml.

    2 NAS Member Editor—professional scientists and active

    researchers.

    3 Independent Peer Reviewers—recognized subject experts.

    PNAS uses a three-tier review process.An NAS member makes the final decision for every paper

    >75%

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    Organized by

    Previously dismissed as cellular debris, extra-

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    both diagnostics and therapeutics.

    Membranemessengers:Extracellularvesicles

    See the full story on page 1349.

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    LIFE SCIENCE TECHNOLOGIES

    EXOSOMES/MICROVESICLES

  • 1349SCIENCE sciencemag.org/custom-publishing

    LIFE SCIENCE TECHNOLOGIES Produced by the Science/AAAS Custom Publishing OfficeEXOSOMES/MICROVESICLES

    In 2007, Johan Skog, a new postdoc in Xandra Breake-

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  • 1350 sciencemag.org/custom-publishing SCIENCE

    LIFE SCIENCE TECHNOLOGIES

    EXOSOMES/MICROVESICLES

    Produced by the Science/AAAS Custom Publishing Office

    Liquid biopsiesDespite the yawning knowledge gap in

    basic vesicle biology, many researchersí

    <��?���=?�?��>�?

    clinical potential.

    Many on the diagnostics front, for instance,

    are pursuing so-called ìliquid biopsies.î Rather

    than diagnosing, staging, and monitoring disease (especially

    cancer) via a solid tumor biopsy or noninvasive imaging,

    �����>?�?����

  • 1351SCIENCE sciencemag.org/custom-publishing

    LIFE SCIENCE TECHNOLOGIES Produced by the Science/AAAS Custom Publishing OfficeEXOSOMES/MICROVESICLES

    patient samples to develop a signature that was better able to

    detect cancer in dense breast tissue than was mammography.

    Similarly, Saugstad has studied the RNA con tent of ce-

    -./-0�����������������0��.���������0�.�������������-.�0��

    Alzheimerís disease. Starting from a set of 756 known human

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    ���.����������.�-���0��0--.���.��������.���.��.�� �!.��

    that miRNAs are regulatory noncoding molecules, that infor-

    mation could identify novel proteins involved in pathophysiol-

    ogy, she says.

    In Boston, Hakho Lee, director of the Biome dical

    Engineering Program at the Center for Systems Biology

    ���"��������.���� .�.-���#0�������������$�����.����0��.-�

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    Lee has developed liquid biopsy analytical tools based on

    multiple principles over the years, including electrochemical

    detection, magnetics, acoustics, and more. His current state-

    of-the-art technology, he says, exploits surface plasmon

    -.�0����.��'����

    SPR is a mature technology that has been commercialized

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    to quantify protein-protein and protein-ligand interactions. To

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    to the opposite face of the gold sensor, that angle changes

    in proportion to the degree of binding, providing a real-time

    readout of molecular interaction.

    In Leeís version of the technology, antibodies are spotted

    on tiny gold sensors in a ìperiodic nanohole array,î which

    ����--���.�0�������-0����������������!.����.��/����0���.�.�

    DOI: 10.1126/science.opms.p1600106

    ��������������������������������������������������������������������

    sensors, their spectral responses change proportionally to

    the degree of binding. Best of all, the measured vesicles can

    ��5�4&�4�����54���3���4��63��6����34����4�4����63��36�4���

    analysis.

    According to Lee, the system is highly scalable. In a proof

    of principle study, for instance, his lab developed a ìnano-

    �����6����4�6�6�4'���#!(���4��63������)�*+,��4�4���6�����4���

    36�����66��6�-)��36�4����4��34��4��6��6��3��������43��4���

    ���4�����4����4�����4������6��36�4���4�6�6�����������34��������4��

    subsequently applied to 20 cancer and 10 control subjects.

    .�����������34��3���4���34���4���34��6��4������4���#!(��������

    Lee notes, with the marker expression dropping in responding

    patients but increasing in nonresponders.

    Therapeutic exosomes Researchers are also investigating exosomes as vehicles

    for delivering therapeutics. EVs, says Joshua Leonard,

    associate professor of Chemical and Biological Engineering

    at Northwestern University, seem to exhibit some of the

    propertiesóespecially low toxicityóthat researchers have been

    struggling to achieve with synthetic vesicles.

    63��������4��34�4�3��43�������6���!/���������4��������3�6�

    using electroporation, or by expressing nucleic acids in EV-

    producing cells. In 2011, Matthew Wood and colleagues at the

    University of Oxford used both approaches to show that they

    could use exosomes to downregulate neuronal gene expression

    in the mouse brain by loading the exosomes with a neuron-

    ��3�4������4����4�������4��������63�����4343����������.����

    result, Leonard says, suggests EVs can overcome at least three

    ��������������3��4����36��������4�5�66��53����5�33�43���4������

    ���4�������4����������5���4�36������������4��������4���43����

    content inside the cells.

    More recently, Leonardís team, led by graduate student

    Michelle Hung, has begun teasing apart the rules governing

    RNA-loading in EVs. The team fused an exosomal protein to

    a bacteriophage protein normally involved in loading nucleic

    acids into viruses, coupled that proteinís signal sequence

    ���3�����6������6���$�434����4������������6���634�������

    RNAs ended up in the resulting particles. All RNAs could be

    loaded, they found, though longer sequences and messenger

    ������4��4���6��6����4���4"����4������014��3�4���6��6�4����

    ���������3�������������&����������4�����6���4�3��4��63��6������

    EVs,î he explains.

    %����������4��6����43�5�4�4$�63���6��6��43���������65�43����6���

    into clinical realities, of course. But given the engagement

    of the research community, expect those advances sooner

    rather than later. ìThereís probably a language here, and weíre

    [only] at the level of knowing something about the alphabet,î

    �6��4�4�� 34��4��4����014��6�2����6����4��3����3���4��6�2��

    ��6����62�����������6���6���63���4���63������ ����4234�����3�

    ing it out.î

    La Trobe Universitywww.latrobe.edu.au

    Northwestern Universitywww.northwestern.edu

    Oregon Health and Science Universitywww.ohsu.edu

    Qiagenwww.qiagen.com

    Scintillon Institutewww.scintillon.org

    �������������

    �����

    ����������������

    University of Texas MD Anderson Cancer Centerwww.mdanderson.org

    University of Utrechtwww.uu.nl

    BD Bioscienceswww.bdbiosciences.com

    Beckman Coulterwww.beckmancoulter.com

    Caris Life Scienceswww.carislifesciences.com

    Center for Systems Biologycsb.mgh.harvard.edu

    Exosome Diagnosticswww.exosomedx.com

    Exosome Scienceswww.exosomesciences.com

    Harvard Medical Schoolhms.harvard.edu

    Insermenglish.inserm.fr

    Institut Curiewww.institut-curie.org

    Learn more about new methods for detecting EVs

    in our recent webinar

    bit.ly/imagef ow

    FEATURED PARTICIPANTS

  • 1352 sciencemag.org/custom-publishing SCIENCE

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