Title:
SYNTHETIC INTRONS FOR TARGETED GENE EXPRESSION
Document Type and Number:
WIPO Patent Application WO/2023/070134
Kind Code:
A3
Abstract:
The disclosure provides artificial nucleic acid introns configured for selective splicing in cells with aberrant RNA splicing activity, e.g., neoplastic cells. The artificial intron can comprise an upstream flanking exon, an upstream intron, an alternatively spliced "cassette" exon, a downstream intron, and a downstream flanking exon. Also provided are constructs integrating the artificial introns with exons in a configuration that, when the artificial intron is spliced out by the aberrant RNA splicing factors, encode a functional protein. Also disclosed are methods that employ the disclosed platform of selective expression, including, targeted gene therapy methods (e.g., in cancers), diagnostics and imaging, and drug screening.
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Inventors:
BRADLEY ROBERT (US)
ABDEL-WAHAB OMAR (US)
STANLEY ROBERT (US)
LIU BO (US)
DE NEEF EMMA (US)
ABDEL-WAHAB OMAR (US)
STANLEY ROBERT (US)
LIU BO (US)
DE NEEF EMMA (US)
Application Number:
PCT/US2022/078615
Publication Date:
May 25, 2023
Filing Date:
October 24, 2022
Export Citation:
Assignee:
FRED HUTCHINSON CANCER CENTER (US)
MEMORIAL SLOAN KETTERING CANCER CENTER (US)
MEMORIAL SLOAN KETTERING CANCER CENTER (US)
International Classes:
C12N15/63; C12N15/67; C12N15/85
Domestic Patent References:
| WO2020033473A1 | 2020-02-13 | |||
| WO2016149455A2 | 2016-09-22 | |||
| WO2022087427A1 | 2022-04-28 |
Foreign References:
| US20100120022A1 | 2010-05-13 |
Other References:
PERRIN G., MORRIS M.A., ANTONARAKIS S.E., BOLTSHAUSER E., HUTTER P.: "Two novel mutations affecting mRNA splicing of the neurofibromatosis type 1 (NF1) gene", HUMAN MUTATION, JOHN WILEY & SONS, INC., US, vol. 7, no. 2, 1 January 1996 (1996-01-01), US , pages 172 - 175, XP093070036, ISSN: 1059-7794, DOI: 10.1002/(SICI)1098-1004(1996)7:2<172::AID-HUMU15>3.0.CO;2-#
ZHANG ET AL.: "Disease-associated mutation in SRSF2 misregulates splicing by altering RNA- binding affinities", PROC NATL ACAD SCI U S A, vol. 112, no. 34, 25 August 2015 (2015-08-25), pages E4726 - 4734, XP055808344, DOI: 10.1073/pnas.1514105112
ZHANG ET AL.: "Disease-associated mutation in SRSF2 misregulates splicing by altering RNA- binding affinities", PROC NATL ACAD SCI U S A, vol. 112, no. 34, 25 August 2015 (2015-08-25), pages E4726 - 4734, XP055808344, DOI: 10.1073/pnas.1514105112
Attorney, Agent or Firm:
POOR, Brian W. et al. (US)
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