Title:
CHROMOSOME THERAPY
Document Type and Number:
WIPO Patent Application WO/2010/014857
Kind Code:
A3
Abstract:
The present invention features compositions and methods for introducing, into cells, nucleic acids whose expression results in chromosomal silencing. The nucleic acids are targeted to specific chromosomal regions where they subsequently reduce the expression of deleterious genes, or cause the death of deleterious cells. Where the nucleic acid sequence is a silencing sequence, it may encode an Xist RNA or other non-coding, silencing RNA. Accordingly, the present invention features, inter alia, nucleic acid constructs that include a transgene (e.g., a silencing sequence encoding an Xist RNA or other non-coding RNA that silences a segment of a chromosome); first and second sequences that direct insertion of the silencing sequence into a targeted chromosome; and, optionally, a selectable marker.
Inventors:
LAWRENCE JEANNE B (US)
HALL LISA L (US)
HALL LISA L (US)
Application Number:
PCT/US2009/052318
Publication Date:
July 01, 2010
Filing Date:
July 30, 2009
Export Citation:
Assignee:
UNIV MASSACHUSETTS (US)
LAWRENCE JEANNE B (US)
HALL LISA L (US)
LAWRENCE JEANNE B (US)
HALL LISA L (US)
International Classes:
C12N15/63; C12N15/90
Other References:
JENNIFER C. CHOW ET AL.: "Inducible XIST-dependent X-chromosome inacti- vation in human somatic cells is reversible", PNAS, vol. 104, no. 24, pages 10104 - 10109
TONI CATHOMEN ET AL.: "Zinc-finger Nucleases: The Next Generation Emerges", MOLECULAR THERAPY, vol. 16, no. 7, 10 June 2008 (2008-06-10), pages 1200 - 1207
N. BROCKDORFF ET AL.: "X chromosome inactivation and the Xist gene", CELL. MOL. LIFE SCI., vol. 54, 1998, pages 104 - 112
GREENE, M. R. ET AL.: "The human XIST gene promoter prevents silencing of an integrated reporter gene", BLOOD, vol. 104, no. 11, 2004, pages ABST. - 2114
CAROLYN J BROWN ET AL.: "The human XIST Gene: Analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus", CELL, vol. 71, 30 October 1992 (1992-10-30), pages 527 - 542
FABIO SAVARESE ET AL.: "Hematopoietic Precursor Cells Transiently Reestablish Permissiveness for X Inactivation", MOLECULAR AND CELLULAR BIOLOGY, vol. 26, no. 19, October 2006 (2006-10-01), pages 7167 - 7177
MATTHEW H. PORTEUS ET AL.: "Mammalian Gene Targeting with Designed Zinc Finger Nucleases", MOLECULAR THERAPY, vol. 13, no. 2, February 2006 (2006-02-01), pages 438 - 446
TONI CATHOMEN ET AL.: "Zinc-finger Nucleases: The Next Generation Emerges", MOLECULAR THERAPY, vol. 16, no. 7, 10 June 2008 (2008-06-10), pages 1200 - 1207
N. BROCKDORFF ET AL.: "X chromosome inactivation and the Xist gene", CELL. MOL. LIFE SCI., vol. 54, 1998, pages 104 - 112
GREENE, M. R. ET AL.: "The human XIST gene promoter prevents silencing of an integrated reporter gene", BLOOD, vol. 104, no. 11, 2004, pages ABST. - 2114
CAROLYN J BROWN ET AL.: "The human XIST Gene: Analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus", CELL, vol. 71, 30 October 1992 (1992-10-30), pages 527 - 542
FABIO SAVARESE ET AL.: "Hematopoietic Precursor Cells Transiently Reestablish Permissiveness for X Inactivation", MOLECULAR AND CELLULAR BIOLOGY, vol. 26, no. 19, October 2006 (2006-10-01), pages 7167 - 7177
MATTHEW H. PORTEUS ET AL.: "Mammalian Gene Targeting with Designed Zinc Finger Nucleases", MOLECULAR THERAPY, vol. 13, no. 2, February 2006 (2006-02-01), pages 438 - 446
Attorney, Agent or Firm:
CREWS, Lee et al. (P.O. Box 1022Minneapolis, MN, US)
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