Means for modulating gene expression
AssigneeUCL Business PLC
InventorsRoberto SIMONE, Rohan DE SILVA
Life of this patent
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Abstract
The present invention provides vectors for delivering to a cell, or expressing in a cell, a therapeutic RNA that is capable of reducing expression of a target gene. Compositions comprising the vectors and comprising the therapeutic RNAs are also provided, as are methods for their use.
Claims49
A vector for delivering to a cell, or expressing in a cell, a therapeutic RNA,
- wherein the therapeutic RNA is capable of reducing expression of a target gene,
- wherein the therapeutic RNA comprises one or more nucleotide sequences that correspond with an antisense long non-coding RNA (AS-lncRNA), wherein the AS-lncRNA comprises a MIR domain in inverse orientation and wherein the AS-lncRNA is encoded by a genomic DNA sequence that is antisense to the target gene, and
- wherein the therapeutic RNA comprises a sequence that corresponds with the MIR domain.
The vector according to any preceding claim, wherein the sequence of the therapeutic RNA that corresponds with the MIR domain comprises a nucleotide sequence having at least 70% identity to a portion of the MIR domain of any one of SEQ ID NOs:
- 1-8 that is able to drive repression of target gene expression, wherein sequence identity is determined across the full length of the portion.
The vector according to any preceding claim, wherein the sequence of the therapeutic RNA that corresponds with the MIR domain comprises a ‘CACCCAC’ and/or a ‘CTGAGGC’ motif.
The vector according to any preceding claim, wherein the target gene encodes tau protein.
A vector for delivering to a cell, or expressing in a cell, a therapeutic RNA,
- wherein the therapeutic RNA is capable of enhancing expression of a target gene,
- wherein the therapeutic RNA comprises one or more nucleotide sequences that correspond with an antisense long non-coding RNA (AS-lncRNA), wherein the AS-lncRNA comprises a MIR domain in direct orientation and wherein the AS-lncRNA is encoded by a genomic DNA sequence that is antisense to the target gene, and
- wherein the therapeutic RNA comprises a sequence that corresponds with the MIR domain.
The vector according to any preceding claim, wherein the sequence of the therapeutic RNA that corresponds with the MIR domain comprises a ‘CACCCAC’ and/or a ‘CUGAGGC’ motif.
The vector according to any preceding claim, wherein the target gene is selected from the group consisting of the target genes listed in Table 1.
The vector according to any preceding claim, wherein the vector comprises a cDNA which encodes the therapeutic RNA.
The vector according to any preceding claim for use in a method of treating the human or animal body by therapy.
The vector according to any preceding claim for use in a method of treating a neurodegenerative condition in a subject, the method comprising the administration of the vector to the subject.
A therapeutic RNA, wherein the therapeutic RNA is capable of reducing expression of a target gene,
- wherein the therapeutic RNA comprises one or more nucleotide sequences that correspond with an antisense long non-coding RNA (AS-lncRNA), wherein the AS-lncRNA comprises a MIR domain in inverse orientation and wherein the AS-lncRNA is encoded by a genomic DNA sequence that is antisense to the target gene, and
- wherein the therapeutic RNA comprises a sequence that corresponds with the MIR domain.
A therapeutic RNA, wherein the therapeutic RNA is capable of enhancing expression of a target gene,
- wherein the therapeutic RNA comprises one or more nucleotide sequences that correspond with an antisense long non-coding RNA (AS-lncRNA), wherein the AS-lncRNA comprises a MIR domain in direct orientation and wherein the AS-lncRNA is encoded by a genomic DNA sequence that is antisense to the target gene, and
- wherein the therapeutic RNA comprises a sequence that corresponds with the MIR domain.
A method of producing a genetically engineered organism, the method comprising introducing the MAPT-AS1 gene into one or more cells of an organism to produce the genetically engineered organism.
A genetically engineered organism that has one or more additional copies of the MAPT-AS1 gene, compared with an equivalent organism that is not genetically engineered to have one or more additional copies of the MAPT-AS1 gene.
A method of producing a lncRNA that is capable of modulating the expression of a protein-coding gene, the method comprising;
- (a) identifying a population of genes that encode a lncRNA, wherein each member of the population comprises a sequence that overlaps a 5′ untranslated region (UTR), an intron, a coding sequence (CDS), and/or a 3′ UTR of a protein-coding gene, and wherein each member of the population is in antisense orientation with respect to the respective protein-coding gene,
- (b) identifying members of the population of genes that encode a lncRNA identified in step (a) that further comprise a MIR domain,
- (c) selecting a gene from the population identified in (b), and
- (d) causing or allowing a transcript of the selected gene to be expressed, which transcript is the produced lncRNA.
Dependencies are inferred from the claim text.