| 摘要 |
The application relates to means, which derive from TAL effectors and TALENs. The structure of the means of the application is especially adapted for partial or full deletion of at least one DNA tandem repeat, more particularly for partial or full deletion of at least one DNA tandem repeat in a double-stranded DNA, more particularly for partial or full deletion of at least one DNA tandem repeat, which is contained in a double-stranded DNA and, which forms a complex secondary structure, such as a hairpin, a triple helix or a tetraplex secondary structure. The means of the application are notably useful in the treatment and/or prevention and/or palliation of a disease or disorder involving at least one DNA tandem repeat, such as DM1, SCA8, SCA12, HDL2, SBMA, HD, DRPLA, SCA1, SCA2, SCA3, SCA6, SCA7, SCA17, PSACH, DM2, SCA10, SPD1, OPMD, CCD, HPE5, HFG syndrome, BPES, EIEE1, FRAXA, FXTAS and FRAXE. |
| 主权项 |
1. A composition or kit comprising a first DNA-binding polypeptide and a second DNA-binding polypeptide,
wherein said first DNA-binding polypeptide is different from said second DNA-binding polypeptide, wherein each of said first and second DNA-binding polypeptides binds to a DNA nucleic acid comprising at least one DNA tandem repeat, wherein the DNA nucleic acid to which said first DNA-binding polypeptide binds is one strand of a double-stranded nucleic acid, wherein the DNA nucleic acid to which said second DNA-binding polypeptide binds is the other strand of the same double-stranded nucleic acid, wherein said double-stranded DNA nucleic acid is a gene involved in a neurological and/or muscular and/or skeletal disorder or disease involving said at least one DNA tandem repeat, wherein each of said first and second DNA-binding polypeptides comprises a TAL effector tandem repeat consisting of adjacent units of TAL effector tandem repeat, wherein the ordered series of RVDs formed by the RVDs respectively contained in said adjacent units of TAL effector tandem repeat, in N- to C-orientation, is an ordered series of amino acids, which determines the recognition of the 5′-3′ nucleotide sequence of a DNA target site contained in the strand of double-stranded DNA nucleic acid to which said DNA-binding polypeptide binds, wherein the sequence of said DNA target site is:
i. a fragment of said strand of double-stranded DNA nucleic acid consisting of a fragment of said at least one DNA tandem repeat, wherein said fragment comprises more than one copy of said DNA sequence unit of said at least one DNA tandem repeat, orii. a fragment of said strand of double-stranded DNA nucleic acid, which starts outside the sequence of said at least one DNA tandem repeat and ends within the sequence of said at least one DNA tandem repeat, or conversely, which starts within the sequence of said at least one DNA tandem repeat and ends outside the sequence of said at least one DNA tandem repeat, wherein each of said first and second DNA-binding polypeptides is directly or indirectly linked to one endonuclease monomer or to one fragment of endonuclease monomer, wherein said fragment of endonuclease monomer still comprises the catalytic domain of said endonuclease monomer, and wherein said first and second DNA-binding polypeptides induce a partial or complete deletion of said at least one DNA tandem repeat. |
