Title:
SYSTEMS AND METHODS FOR AMPLIFICATION AND PHAGE DISPLAY
Document Type and Number:
WIPO Patent Application WO/2012/047324
Kind Code:
A3
Abstract:
The present invention generally relates to amplification of biological entities, for example, for phage display. In one aspect, members of a library of biological entities are encapsulated in separate compartments (e.g., in separate microfluidic droplets) and amplified. As a specific example, by putting members of a phage display library into microfluidic droplets such that no droplet contains more than one member of the library, the library can be amplified without any substantial changes in growth rates or population distributions, or other artifacts created due to differences in growth rates or amplification between different members of the library. In some cases, the volume of the compartments can be used to control the copy number of a biological entity during amplification. In certain cases, biological entities with different amplification rates can be amplified independently of each other. In some embodiments, the ratio of a rapidly amplifying biological entity to a slowly amplifying biological entity can be controlled. This can be advantageous, for example, in preserving diversity within a library by preventing rapidly amplifying biological entities from outcompeting slowly amplifying biological entities. For example, certain methods and systems of the invention can be useful in situations where preferential amplification of library members can present a problem.
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Inventors:
DERDA RATMIR (US)
TANG SINDY K Y (US)
WHITESIDES GEORGE M (US)
TANG SINDY K Y (US)
WHITESIDES GEORGE M (US)
Application Number:
PCT/US2011/039932
Publication Date:
September 07, 2012
Filing Date:
June 10, 2011
Export Citation:
Assignee:
HARVARD COLLEGE (US)
DERDA RATMIR (US)
TANG SINDY K Y (US)
WHITESIDES GEORGE M (US)
DERDA RATMIR (US)
TANG SINDY K Y (US)
WHITESIDES GEORGE M (US)
International Classes:
C12N15/10; C40B40/02; C40B50/06
Domestic Patent References:
| WO2009011808A1 | 2009-01-22 | |||
| WO2005030957A1 | 2005-04-07 |
Other References:
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CLAUSELL-TORMOS J ET AL: "Droplet-Based Microfluidic Platforms for the Encapsulation and Screening of Mammalian Cells and Multicellular Organisms", CHEMISTRY AND BIOLOGY, CURRENT BIOLOGY, LONDON, GB, vol. 15, no. 5, 19 May 2008 (2008-05-19), pages 427 - 437, XP022659855, ISSN: 1074-5521, [retrieved on 20080512], DOI: 10.1016/J.CHEMBIOL.2008.04.004
BERTSCHINGER J ET AL: "Covalent DNA display as a novel tool for directed evolution of protein in vitro", PROTEIN ENGINEERING, DESIGN AND SELECTION, OXFORD JOURNAL, LONDON, GB, vol. 17, no. 9, 2 November 2004 (2004-11-02), pages 699 - 707, XP002312485, ISSN: 1741-0126, DOI: 10.1093/PROTEIN/GZH082
DOI N ET AL: "STABLE: protein-DNA fusion system for screening of combinatorial protein libraries in vitro", FEBS LETTERS, ELSEVIER, AMSTERDAM, NL, vol. 457, no. 2, 27 August 1999 (1999-08-27), pages 227 - 230, XP004260157, ISSN: 0014-5793, DOI: 10.1016/S0014-5793(99)01041-8
RODI D J ET AL: "Quantitative Assessment of Peptide Sequence Diversity in M13 Combinatorial Peptide Phage Display Libraries", JOURNAL OF MOLECULAR BIOLOGY, ACADEMIC PRESS, UNITED KINGDOM, vol. 322, no. 5, 4 October 2002 (2002-10-04), pages 1039 - 1052, XP004449793, ISSN: 0022-2836, DOI: 10.1016/S0022-2836(02)00844-6
PETRENKO V A ET AL: "A library of organic landscapes on filamentous phage", PROTEIN ENGINEERING, OXFORD UNIVERSITY PRESS, SURREY, GB, vol. 9, no. 9, 1 January 1996 (1996-01-01), pages 797 - 801, XP002209669, ISSN: 0269-2139
IONNOLO G ET AL: "CONSTRUCTION, EXPLOITATION AND EVOLUTION OF A NEW PEPTIDE LIBRARY DISPLAYED AT HIGH DENSITY BY FUSION TO THE MAJOR COAT PROTEIN OF FILAMENTOUS PHAGE", BIOLOGICAL CHEMISTRY, WALTER DE GRUYTER GMBH & CO, BERLIN, DE, vol. 378, no. 6, 1 June 1997 (1997-06-01), pages 517 - 521, XP001063279, ISSN: 1431-6730
JING-MIN ZHOU ET AL: "A novel strategy by the action of ricin that connects phenotype and genotype without loss of the diversity of libraries", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, AMERICAN CHEMICAL SOCIETY, WASHINGTON, DC; US, vol. 124, no. 4, 1 January 2002 (2002-01-01), pages 538 - 543, XP002956621, ISSN: 0002-7863, DOI: 10.1021/JA011885X
BRAMMER ET AL: "A target-unrelated peptide in an M13 phage display library traced to an advantageous mutation in the gene II ribosome-binding site", ANALYTICAL BIOCHEMISTRY, ACADEMIC PRESS INC, NEW YORK, vol. 373, no. 1, 14 October 2007 (2007-10-14), pages 88 - 98, XP022575083, ISSN: 0003-2697, DOI: 10.1016/J.AB.2007.10.015
DERDA RATMIR ET AL: "High-Throughput Discovery of Synthetic Surfaces That Support Proliferation of Pluripotent Cells", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 132, no. 4, February 2010 (2010-02-01), pages 1289 - 1295, XP002672052, ISSN: 0002-7863
DERDA RATMIR ET AL: "Uniform amplification of phage with different growth characteristics in individual compartments consisting of monodisperse droplets.", ANGEWANDTE CHEMIE (INTERNATIONAL ED. IN ENGLISH) 19 JUL 2010 LNKD- PUBMED:20583018, vol. 49, no. 31, 25 June 2010 (2010-06-25), pages 5301 - 5304, XP002672053, ISSN: 1521-3773
DERDA RATMIR ET AL: "Diversity of phage-displayed libraries of peptides during panning and amplification.", MOLECULES (BASEL, SWITZERLAND) 2011 LNKD- PUBMED:21339712, vol. 16, no. 2, 21 February 2011 (2011-02-21), pages 1776 - 1803, XP009157587, ISSN: 1420-3049
CLAUSELL-TORMOS J ET AL: "Droplet-Based Microfluidic Platforms for the Encapsulation and Screening of Mammalian Cells and Multicellular Organisms", CHEMISTRY AND BIOLOGY, CURRENT BIOLOGY, LONDON, GB, vol. 15, no. 5, 19 May 2008 (2008-05-19), pages 427 - 437, XP022659855, ISSN: 1074-5521, [retrieved on 20080512], DOI: 10.1016/J.CHEMBIOL.2008.04.004
BERTSCHINGER J ET AL: "Covalent DNA display as a novel tool for directed evolution of protein in vitro", PROTEIN ENGINEERING, DESIGN AND SELECTION, OXFORD JOURNAL, LONDON, GB, vol. 17, no. 9, 2 November 2004 (2004-11-02), pages 699 - 707, XP002312485, ISSN: 1741-0126, DOI: 10.1093/PROTEIN/GZH082
DOI N ET AL: "STABLE: protein-DNA fusion system for screening of combinatorial protein libraries in vitro", FEBS LETTERS, ELSEVIER, AMSTERDAM, NL, vol. 457, no. 2, 27 August 1999 (1999-08-27), pages 227 - 230, XP004260157, ISSN: 0014-5793, DOI: 10.1016/S0014-5793(99)01041-8
RODI D J ET AL: "Quantitative Assessment of Peptide Sequence Diversity in M13 Combinatorial Peptide Phage Display Libraries", JOURNAL OF MOLECULAR BIOLOGY, ACADEMIC PRESS, UNITED KINGDOM, vol. 322, no. 5, 4 October 2002 (2002-10-04), pages 1039 - 1052, XP004449793, ISSN: 0022-2836, DOI: 10.1016/S0022-2836(02)00844-6
PETRENKO V A ET AL: "A library of organic landscapes on filamentous phage", PROTEIN ENGINEERING, OXFORD UNIVERSITY PRESS, SURREY, GB, vol. 9, no. 9, 1 January 1996 (1996-01-01), pages 797 - 801, XP002209669, ISSN: 0269-2139
IONNOLO G ET AL: "CONSTRUCTION, EXPLOITATION AND EVOLUTION OF A NEW PEPTIDE LIBRARY DISPLAYED AT HIGH DENSITY BY FUSION TO THE MAJOR COAT PROTEIN OF FILAMENTOUS PHAGE", BIOLOGICAL CHEMISTRY, WALTER DE GRUYTER GMBH & CO, BERLIN, DE, vol. 378, no. 6, 1 June 1997 (1997-06-01), pages 517 - 521, XP001063279, ISSN: 1431-6730
JING-MIN ZHOU ET AL: "A novel strategy by the action of ricin that connects phenotype and genotype without loss of the diversity of libraries", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, AMERICAN CHEMICAL SOCIETY, WASHINGTON, DC; US, vol. 124, no. 4, 1 January 2002 (2002-01-01), pages 538 - 543, XP002956621, ISSN: 0002-7863, DOI: 10.1021/JA011885X
BRAMMER ET AL: "A target-unrelated peptide in an M13 phage display library traced to an advantageous mutation in the gene II ribosome-binding site", ANALYTICAL BIOCHEMISTRY, ACADEMIC PRESS INC, NEW YORK, vol. 373, no. 1, 14 October 2007 (2007-10-14), pages 88 - 98, XP022575083, ISSN: 0003-2697, DOI: 10.1016/J.AB.2007.10.015
DERDA RATMIR ET AL: "High-Throughput Discovery of Synthetic Surfaces That Support Proliferation of Pluripotent Cells", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 132, no. 4, February 2010 (2010-02-01), pages 1289 - 1295, XP002672052, ISSN: 0002-7863
DERDA RATMIR ET AL: "Uniform amplification of phage with different growth characteristics in individual compartments consisting of monodisperse droplets.", ANGEWANDTE CHEMIE (INTERNATIONAL ED. IN ENGLISH) 19 JUL 2010 LNKD- PUBMED:20583018, vol. 49, no. 31, 25 June 2010 (2010-06-25), pages 5301 - 5304, XP002672053, ISSN: 1521-3773
DERDA RATMIR ET AL: "Diversity of phage-displayed libraries of peptides during panning and amplification.", MOLECULES (BASEL, SWITZERLAND) 2011 LNKD- PUBMED:21339712, vol. 16, no. 2, 21 February 2011 (2011-02-21), pages 1776 - 1803, XP009157587, ISSN: 1420-3049
Attorney, Agent or Firm:
RESNICK, David S. et al. (100 Summer StreetBoston, Massachusetts, US)
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