Methods and nucleic acid molecules for aav vector selection
US-2024417717-A1 · Dec 19, 2024 · US
US10227609B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-10227609-B2 |
| Application number | US-201314355691-A |
| Country | US |
| Kind code | B2 |
| Filing date | Jan 25, 2013 |
| Priority date | Jan 27, 2012 |
| Publication date | Mar 12, 2019 |
| Grant date | Mar 12, 2019 |
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Described are methods for efficiently down regulating the expression of a gene of interest in a cell by use of a modified rodent parvovirus that contains an expressible target specific nucleic acid, preferably an shRNA expression cassette. Also described are cells or organisms comprising said parvovirus.
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The invention claimed is: 1. A modified parvovirus having a modified H-1 parvoviral genome comprising a non-coding region downstream of a parvovirus VP gene, wherein the modified H-1 parvoviral genome comprises the nucleotide sequence of SEQ ID NO:15 comprising the following mutations: (i) a deletion of nucleotides 2022-2135 of SEQ ID NO:15; and (ii) an insertion within the non-coding region downstream of the parvovirus VP gene, wherein the insertion is a nucleic acid molecule encoding a short hairpin RNA (shRNA) transcript under the control of a RNA polymerase III H1 promoter, wherein the shRNA is specific to a target gene, and wherein the modified parvovirus is capable of replicating and propagating in a cell autonomously. 2. The modified parvovirus of claim 1 , wherein the target gene is a disease-causing gene. 3. The modified parvovirus of claim 2 , wherein the disease-causing gene is a pathogenic animal virus gene, a cancer-related gene, an oncogene, anti-apoptotic gene, a gene critical for tumour cell growth, metastasis, angiogenesis or chemioresistance, an immunomodulatory gene, or a gene encoding a cytokine, growth factor, enzyme or transcription factor. 4. A composition comprising the modified parvovirus of claim 1 , further comprising a solvent suitable for intravenous (i.v.), intratumoral or endobronchial administration. 5. A cell containing the modified parvovirus of claim 1 .
viral genome or elements thereof as genetic vector · CPC title
Specially adapted vectors · CPC title
Special delivery means, e.g. tissue-specific · CPC title
Stem-loop; Hairpin · CPC title
Viral vectors · CPC title
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