METHOD TO OVERCOME DNA CHEMICAL MODIFICATIONS SENSITIVITY OF ENGINEERED TALE DNA BINDING DOMAINS

摘要

The present invention relates to polypeptides and more particularly to Transcription Activator-Like Effector derived proteins that allow to efficiently target and/or process nucleic acids. Particularly, the present invention reports the characterization of TALE derived proteins that can efficiently target methylated DNA. The present invention more specifically relates to TALE derived proteins that allow activation of methylated promoters responsible for gene silencing.

主权项

1. A method for synthesizing a transcription activator-like effector (TALE) protein to target nucleic acid sequence comprising a chemically modified nucleic acid base, said method comprising assembling a plurality of TALE-like repeat sequences, each of said sequences comprising a repeat variable-diresidue (RVD) specific to each nucleic acid base of said sequence, wherein the RVD(s) that specifically targets the chemically modified nucleic acid base within said nucleic acid target sequence are selected from X* or **, where X represents one amino acid residue selected from the group of A, G, V, L, I, M, S, T, C, P, D, E, F, Y, W, Q, N, H, R and K and * represents a gap in one position of the RVD.