Compositions and methods specifically targeting the apolipoprotein e4 (apoe4) and uses thereof in apoe4 associated conditions
AssigneeRamof at Tel-Aviv University Ltd.
InventorsDavid OFFEN, Roy RABINOWITZ, Tall BEN-ZUR, Daniel MICHAELSON
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Abstract
The invention relates to improvement and therapy of neuronal conditions involving neurodegenerative, inflammatory and vascular conditions. More specifically, the invention provides compositions and methods for specific targeted elimination of apolipoprotein E4 (apoE4), and uses thereof in the treatment and prevention of ApoE4 associated conditions.
Claims32
A method for targeted elimination of at least one Apolipoprotein E (ApoE) pathogenic protein in a cell, the method comprising the step of contacting said cell with an effective amount of:
- (a) at least one polypeptide comprising at least one clustered regulatory interspaced short palindromic repeat (CRISPR) associated (cas) protein, or any nucleic acid encoding said polypeptide, wherein said cas protein specifically recognizes the 5′-NGCG-3′ proto-spacer adjacent motif (PAM);
- and
- (b) at least one nucleic acid sequence comprising at least one guide RNA (gRNA) that targets a protospacer located upstream to said PAM within at least ApoE pathogenic allele encoding said at least one pathogenic ApoE protein, or any nucleic acid sequence encoding said gRNA;
- or with a kit, composition or vehicle comprising (a) and (b).
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A pharmaceutical composition comprising a therapeutic effective amount of:
- (a) at least one polypeptide comprising at least one Cas protein, or any nucleic acid encoding said polypeptide, wherein said Cas protein specifically recognizes the 5′-NGCG-3′ PAM;
- and
- (b) at least one nucleic acid sequence comprising at least one gRNA that targets a protospacer located upstream to said PAM within a pathogenic allele of ApoE or any nucleic acid sequence encoding said gRNA;
- or
- (c) a kit comprising (a) and (b);
- said composition optionally further comprises at least one of pharmaceutically acceptable carrier/s, diluent/s and/or excipient/s.
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A diagnostic kit comprising:
- a. at least one polypeptide comprising at least one dCas, or any nucleic acid encoding said polypeptide, wherein said dCas protein specifically recognizes the 5′-NGCG-3′ PAM;
- and
- b. at least one gRNA that targets a protospacer located upstream to said PAM within the ApoE pathogenic allele, or any nucleic acid sequence encoding said gRNA;
- wherein at least one of said dCas of (a) and said gRNA of (b) is directly or indirectly attached to at least one detectable moiety, wherein said ApoE pathogenic allele is ApoEε4 allele.
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Dependencies are inferred from the claim text.