Title:
NUCLEIC ACID SYSTEMS THAT ENABLE BACTERIA TO SPECIFICALLY TARGET SOLID TUMORS VIA GLUCOSE-DEPENDENT VIABILITY
Document Type and Number:
WIPO Patent Application WO/2019/047166
Kind Code:
A1
Abstract:
Provided is a nucleic acid system introduced into a bacterial strain to generate a genetically engineered bacterial strain that grows in solid tumors but does not grow in non-tumor tissues, the nucleic acid system comprising: a first DNA fragment that encodes a toxin gene that expresses a toxin that kills the genetically engineered bacterial strain; a second DNA fragment that encodes an antidote gene that expresses an antidote that negates the toxin; a first promotor that controls transcription of the antidote gene, such that glucose represses the transcription of the antidote gene; and a first constitutive promoter that causes constitutive expression of the toxin gene; wherein the second DNA fragment is transcribed in the solid tumors but not transcribed in the non-tumor tissues.
Inventors:
JIN YE (CN)
Application Number:
PCT/CN2017/101069
Publication Date:
March 14, 2019
Filing Date:
September 08, 2017
Export Citation:
Assignee:
NEW PORTAL LTD (CN)
International Classes:
C12N15/63; C12N1/21; C12R1/01
Domestic Patent References:
| WO2012087483A1 | 2012-06-28 | |||
| WO2001005421A1 | 2001-01-25 |
Foreign References:
| US9198950B2 | 2015-12-01 | |||
| CN1688699A | 2005-10-26 | |||
| CN106676119A | 2017-05-17 | |||
| US9555127B2 | 2017-01-31 |
Other References:
Z. DOUVLIS: "Interference of amino acid patterns and tissue-specific amino acids absorption dominance under the influence of tumor cell protein degradation toxins", MEDICAL HYPOTHESES, vol. 53, no. 5, 31 December 1999 (1999-12-31), pages 450 - 457, XP055581820, ISSN: 0306-9877
GUILLERMO DE LA CUEVA-MENDEZ ET AL.: "Regulatable killing of eukaryotic cells by the prokaryotic proteins Kid and Kis", THE EMBO JOURNAL, vol. 22, no. 2, 31 December 2003 (2003-12-31), pages 246 - 251, XP002421993, ISSN: 0261-4189, DOI: doi:10.1093/emboj/cdg026
LUKASZ WIETESKA ET AL.: "Toxins VapC and PasB from prokaryotic TA modules remain active mammalian cancer cells", TOXINS, vol. 6, no. 10, 30 September 2014 (2014-09-30), pages 2948 - 2961, XP055581830, ISSN: 2072-6651
YEO, CHEWCHIENG ET AL.: "Heterologous expression of toxins from bacterial Toxin-Antitoxin Systems in eukaryotic cells: strategies and applications", TOXINS, vol. 8, no. 49, 19 February 2016 (2016-02-19), pages 1 - 16, XP055581850, ISSN: 2072-6651
See also references of EP 3679142A4
GUILLERMO DE LA CUEVA-MENDEZ ET AL.: "Regulatable killing of eukaryotic cells by the prokaryotic proteins Kid and Kis", THE EMBO JOURNAL, vol. 22, no. 2, 31 December 2003 (2003-12-31), pages 246 - 251, XP002421993, ISSN: 0261-4189, DOI: doi:10.1093/emboj/cdg026
LUKASZ WIETESKA ET AL.: "Toxins VapC and PasB from prokaryotic TA modules remain active mammalian cancer cells", TOXINS, vol. 6, no. 10, 30 September 2014 (2014-09-30), pages 2948 - 2961, XP055581830, ISSN: 2072-6651
YEO, CHEWCHIENG ET AL.: "Heterologous expression of toxins from bacterial Toxin-Antitoxin Systems in eukaryotic cells: strategies and applications", TOXINS, vol. 8, no. 49, 19 February 2016 (2016-02-19), pages 1 - 16, XP055581850, ISSN: 2072-6651
See also references of EP 3679142A4
Attorney, Agent or Firm:
SHENZHEN ZHONGLIAN PATENT AGENCY CO., LTD et al. (CN)
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