Methods for increasing specificity of RNA-guided genome editing, e.g., editing using CRISPR/Cas9 systems.

Methods for increasing specificity of RNA-guided genome editing, e.g., editing using CRISPR/Cas9 systems.

Methods and constructs for RNA-guided targeting of heterologous functional domains such as transcriptional activators to specific genomic loci.

Methods for increasing specificity of RNA-guided genome editing, e.g., editing using CRISPR/Cas9 systems.

Methods for increasing specificity of RNA-guided genome editing, e.g., editing using CRISPR/Cas9 systems, using truncated guide RNAs (tru-gRNAs).

Methods for increasing specificity of RNA-guided genome editing, e.g., editing using CRISPR/Cas9 systems.

Methods for increasing specificity of RNA-guided genome editing, e.g., editing using CRISPR/Cas9 systems, using truncated guide RNAs (tru-gRNAs).

The present invention relates to a polypeptide which is a temperature-modulated ion channel, wherein said ion channel is a channel comprising four subunits which associate to form a homo- or hetero-tetramer, preferably is a potassium channel, wherein said polypeptide comprises at least one peptide comprising at least one portion of one of said subunits and a portion of the cytoplasmic C-terminal domain of the bacterial voltage-gated sodium channel BacNav, wherein said portion comprises at least one mutation in one of the amino acids in position 267, 271 or 274, wherein said numbering is read with reference to the voltage-gated sodium channel BacNav, SEQ ID NO: 5. The present invention further relates to the use of said polypeptide in the treatment of a condition modulated by potassium channel activity, selected from the group comprising: neuromyotonia, episodic ataxia type 1, hereditary deafness syndromes, benign familial neonatal seizures and periodic hypokalemic paralysis, neuropathic pain, diabetic neuropathic pain, trauma (thoracic surgery), glioblastoma, skin diseases, in particular originating from keratinocyte dysfunctions.