The invention generally relates to isolated nucleic acid ligands that are neutral under physiological conditions.

An object of the present invention is to provide a circular single-stranded nucleic acid, and a method for preparing the same and a method for using the same. A circular single-stranded nucleic acid according to one embodiment of the present invention is a circular single-stranded nucleic acid for determining a target base on a genomic DNA, and includes a first single-stranded nucleic acid which has the target base or a complementary base thereto and is a part of one of the strands of the genomic DNA, and a second single-stranded nucleic acid which has an index sequence to serve as an index of a cell, from which the genomic DNA is derived, or a complementary sequence thereto.

Provided herein are hybrid oligonucleotides comprising a region that promotes cleavage of a nucleic acid and a region that protects a nucleic acid from exonuclease activity. Such hybrid oligonucleotides are useful for modulating the expression of genes. Related compositions and methods are also provided. In some embodiments, methods are provided for treating a disease, such as by administering a hybrid oligonucleotide.

The present disclosure generally relates to compositions and methods for improving the efficiency of homologous recombination. In particular, the disclosure relates to reagents and the use of such reagents.

The invention generally relates to isolated nucleic acid ligands that are neutral under physiological conditions.

Peptide nucleic acid (PNA) oligomers that target the -globin gene and can increase the frequency of recombination of donor oligonucleotide at the site of a Sickle Cell Disease mutation are provided. Nanoparticle formulations for delivering the PNA oligomers and donor oligonucleotides, and potentiating agents for increase the frequency of recombination of the donor oligonucleotide are also provided. Methods of using the PNA oligomers, donor oligonucleotides, nanoparticles, and potentiating agents for treating Sickle Cell Disease are also provided.

Compositions for improved gene editing and methods of use thereof are disclosed. In a preferred method, gene editing involves use of a cell-penetrating anti-DNA antibody, such as 3E10, as a potentiating agent to enhance gene editing by nucleases and triplex forming oligonucleotides. Genomic modification occurs at a higher frequency when cells are contacted with the potentiating agent and nuclease or triplex forming oligonucleotide, as compared to the absence of the potentiating agent. The methods are suitable for both ex vivo and in vivo approaches to gene editing and are useful for treating a subject with a genetic disease or disorder. Nanoparticle compositions for intracellular delivery of the gene editing compositions are provided and are particularly advantageous for use with in vivo applications.