The present disclosure provides DNA-guided CRISPR systems; polynucleotides comprising DNA, RNA and mixtures thereof for use with CRISPR systems; and methods of use involving such polynucleotides and DNA-guided CRISPR systems.

An RNAi molecule comprising the nucleotide sequence of SEQ ID NO: 1 in an antisense strand; and a method for treating a disease, comprising administering an effective amount of the RNAi molecule to a subject in need thereof.

An RNAi molecule comprising the nucleotide sequence of SEQ ID NO: 1 in an antisense strand; and a method for treating a disease, comprising administering an effective amount of the RNAi molecule to a subject in need thereof.

The present invention relates to methods and compositions for editing a MECP2 polynucleotide, e.g., a MECP2 polynucleotide comprising a SNP associated with Rett syndrome. The invention also relates to methods and compositions for treating or preventing Rett syndrome in a subject.

The present invention relates to methods and compositions for editing a MECP2 polynucleotide, e.g., a MECP2 polynucleotide comprising a SNP associated with Rett syndrome. The invention also relates to methods and compositions for treating or preventing Rett syndrome in a subject.

The present invention relates to methods and compositions for editing a TMC1 polynucleotide, e.g., a TMC1 polynucleotide comprising a SNP associated with autosomal recessive non-syndromic hearing loss. The invention also relates to methods and compositions for treating or preventing autosomal recessive non-syndromic hearing loss in a subject.

The present invention relates to methods and compositions for editing a TMC1 polynucleotide, e.g., a TMC1 polynucleotide comprising a SNP associated with autosomal recessive non-syndromic hearing loss. The invention also relates to methods and compositions for treating or preventing autosomal recessive non-syndromic hearing loss in a subject.

The present invention relates to RNAi constructs for reducing expression of the ASGR1 gene. Methods of using such RNAi constructs to treat or prevent cardiovascular disease, such as coronary artery disease and myocardial infarction, and to reduce serum non-HDL cholesterol levels are also described.

The present invention relates to RNAi constructs for reducing expression of the ASGR1 gene. Methods of using such RNAi constructs to treat or prevent cardiovascular disease, such as coronary artery disease and myocardial infarction, and to reduce serum non-HDL cholesterol levels are also described.

The present disclosure provides CRISPR/Cas9 ribonucleoprotein compositions comprising chemically modified CRISPR RNA (crRNA) guide and trans-acting CRISPR RNA (tracrRNA) components. Methods of using the disclosed CRISPR/Cas9 ribonucleoprotein compositions are also provided.