Liver-specific regulatory nucleic acid sequences
AssigneeAskbio Inc.
InventorsLester SUAREZ, Juan Manuel IGLESIAS GONZALEZ, Flavia SCIALPI
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Abstract
The present invention relates to regulatory nucleic acid sequences, in particular short liver-specific cis-regulatory elements, cis-regulatory modules, promoters and other such nucleic acid sequences, that are short and capable of enhancing liver-specific expression of genes. The invention also relates to expression constructs, vectors and cells comprising such short liver-specific regulatory nucleic acid sequences, and to methods of their use. The liver-specific regulatory nucleic acid sequences are of particular utility for gene therapy applications, but also find utility in other areas such as bioprocessing and biotechnology.
Claims39
A synthetic liver-specific promoter comprising a combination of one or more cis-regulatory elements (CREs) or functional variants of any thereof operably linked to a promoter element (or a functional variant of any thereof) selected from the group consisting of:
- CRE0051, CRE0042, CRE0059 and 5′UTR;
- CRE0051, CRE0058 and CRE0070;
- CRE0051, CRE0058 and CRE0071;
- CRE0042 and CRE0099;
- CRE0042 and CRE0073;
- CRE0051 and CRE0099;
- CRE0051 and CRE0073;
- CRE0051, CRE0058 and CRE0054;
- CRE0094 and CRE0052;
- CRE0056, CRE0094 and CRE0052;
- CRE0056, CRE0094 and CRE0059;
- CRE0048, CRE0056 and CRE0054;
- CRE0048, CRE0056 and CRE0052;
- and
- CRE0048, CRE0056 and CRE0059.
The synthetic liver-specific promoter of any preceding claim which has a length of 350 or fewer nucleotides, 340, 330, 320, 310, 300, 290, 280, 270, 260, 250, 240, 230, 220 or fewer nucleotides.
A synthetic liver-specific promoter comprising one of the following promoter elements:
- CRE0059, CRE0070, CRE0071, CRE0054, CRE0073, CRE0099 and CRE0052 or a functional variant thereof.
A promoter element comprising any one of CRE0059, CRE0070, CRE0071, CRE0054, CRE0073, CRE0099 and CRE0052 or a functional variant thereof.
A liver-specific CRE selected from the group consisting of:
- CRE0051, CRE0042, CRE0058, CRE0048, CRE0094 and CRE0056, or a functional variant of any thereof, wherein the functional variant of any of said CREs comprises a sequence that is at least 70% identical to a reference synthetic liver-specific CRE, more preferably at least 80%, 90%, 95%, 96%, 97%, 98% or 99% identical to the reference synthetic liver-specific CRE.
Dependencies are inferred from the claim text.