Regeneration of surface antigen-negative cells
AssigneeCorrectsequence Therapeutics
InventorsLijie WANG, Yichuan WANG, Suling LI, Jia CHEN, Li YANG
Life of this patent
Estimating the term…
Abstract
Provided are gene editing technologies, including specifically designed and tested guide RNA sequences for improved base editors, useful for disrupting the expression of genes, such as CD33, CD123, CD47, CD45 and CLL1, in a cell. Such methods and edited cells are useful in reducing the toxicity associated with therapies targeting such cell surface antigens, such as those for treating acute myeloid leukemia.
Claims32
A method for reducing the biological activity of the CD33, CD123, CD47, CD45 or CLL1 gene in a cell to reduce toxicity in a patient undergoing a therapy targeting a cell surface antigen on a cancer cell, comprising administering to the patient, comprising introducing into the cell a CRISPR-associated (Cas) protein, a nucleobase deaminase, a single-guide RNA (sgRNA), and a helper single-guide RNA (hsgRNA), wherein the Cas protein, the nucleobase deaminase, the sgRNA, and the hsgRNA are preferably introduced into the cell by one or more encoding polynucleotides, and wherein the sgRNA and the hsgRNA, respectively, comprise the nucleic acid sequences selected from:
- sgRNA
- hsgRNA
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A method for reducing the biological activity of the CD33 gene in a cell, comprising introducing into the cell a CRISPR-associated (Cas) protein, a nucleobase deaminase, a single-guide RNA (sgRNA), and a helper single-guide RNA (hsgRNA), wherein the Cas protein, the nucleobase deaminase, the sgRNA, and the hsgRNA are preferably introduced into the cell by one or more encoding polynucleotides, and wherein the sgRNA and the hsgRNA, respectively, comprise the nucleic acid sequences selected from:
- sgRNA
- hsgRNA
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- 57-62
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- 69-74
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A method for reducing the biological activity of the CD123 gene in a cell, comprising introducing into the cell a CRISPR-associated (Cas) protein, a nucleobase deaminase, a single-guide RNA (sgRNA), and a helper single-guide RNA (hsgRNA), wherein the Cas protein, the nucleobase deaminase, the sgRNA, and the hsgRNA are preferably introduced into the cell by one or more encoding polynucleotides, and wherein the sgRNA and the hsgRNA, respectively, comprise the nucleic acid sequences selected from:
- sgRNA
- hsgRNA
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A method for reducing the biological activity of the CD47 gene in a cell, comprising introducing into the cell a CRISPR-associated (Cas) protein, a nucleobase deaminase, a single-guide RNA (sgRNA), and a helper single-guide RNA (hsgRNA), wherein the Cas protein, the nucleobase deaminase, the sgRNA, and the hsgRNA are preferably introduced into the cell by one or more encoding polynucleotides, and wherein the sgRNA and the hsgRNA, respectively, comprise the nucleic acid sequences selected from:
- sgRNA
- hsgRNA
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- 304-306
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- 309-310
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- 315-318.
A method for reducing the biological activity of the CD45 gene in a cell, comprising introducing into the cell a CRISPR-associated (Cas) protein, a nucleobase deaminase, a single-guide RNA (sgRNA), and a helper single-guide RNA (hsgRNA), wherein the Cas protein, the nucleobase deaminase, the sgRNA, and the hsgRNA are preferably introduced into the cell by one or more encoding polynucleotides, and wherein the sgRNA and the hsgRNA, respectively, comprise the nucleic acid sequences selected from:
- sgRNA
- hsgRNA
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- 35
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- 321-322
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- 378-382
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- 47
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A method for reducing the biological activity of the CLL1 gene in a cell, comprising introducing into the cell a CRISPR-associated (Cas) protein, a nucleobase deaminase, a single-guide RNA (sgRNA), and a helper single-guide RNA (hsgRNA), wherein the Cas protein, the nucleobase deaminase, the sgRNA, and the hsgRNA are preferably introduced into the cell by one or more encoding polynucleotides, and wherein the sgRNA and the hsgRNA, respectively, comprise the nucleic acid sequences selected from:
- sgRNA
- hsgRNA
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- 48
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- 389-392
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- 49
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- 396-398
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- 402-404.
One or more polynucleotides encoding a CRISPR-associated (Cas) protein, a nucleobase deaminase, a single-guide RNA (sgRNA), and a helper single-guide RNA (hsgRNA), wherein the sgRNA and the hsgRNA are selected from the sequences from Table 1.
Dependencies are inferred from the claim text.