Described herein are molecules for editing a cell. The molecules described herein generally comprise the following covalently-linked components and a nucleic acid encoding a guide RNA (gRNA) sequence targeting a target region in a cell and a region homologous to the target region comprising a change in sequence relative to the target region.

The disclosure relates to synthetic oligonucleotides that are unique in that they are RNA molecules that have the capacity to form a hydrogel. Also disclosed are DNA oligonucleotides that encode the RNA oligos so that the oligos can be prepared using in vitro transcription. The disclosure further pertains to pharmaceutical compositions comprising these hydrogels.

Methods and compositions for modulation of the activity of alpha thalassemia/mental retardation syndrome X-linked (ATRX), e.g., modulation of DNA-ATRX or RNA-ATRX interactions, and methods for identifying and using compounds that modulate DNA-ATRX or RNA-ATRX interactions, as well as the compounds themselves.

The invention relates to a method of identifying stereodefined phosphorothioate oligonucleotide variants with reduced toxicity by creating and screening libraries of stereodefined chiral phosphorothioate variants for compounds with reduced toxicity, either in vitro or in vivo.

Compositions and methods are provided for forming a single RNA polynucleotide from a plurality of DNA oligonucleotides in a single reaction chamber using combined reagents in a single step reaction. DNA polymerase, RNA polymerase and single stranded (ss) DNA oligonucleotides are combined where each DNA oligonucleotide has one or more sequence modules, wherein one sequence module in the first ss DNA oligonucleotide is complementary to a sequence module at the 3′ end of the second ss DNA oligonucleotide; and wherein a second module on the first ss DNA oligonucleotide is an RNA polymerase promoter sequence; and forming a single RNA polynucleotide, excluding the RNA promoter sequence, derived from the first and second DNA oligonucleotides

Provided are internalizing nucleic acid molecules (“iNA”) that can bind and internalize into target cells containing a cell surface molecule to which the iNA can bind; an iNA further modified to include at least one chemical modification, wherein the at least one modification is selected from the group consisting of a chemical substitution in the nucleic acid sequence of the iNA, incorporation of a modified nucleotide into the iNA, conjugation to a linker, and conjugation to at least one effector moiety comprising one or more of a drug or a detectable moiety or a combination thereof; and methods of using modified iNA to deliver at least one effector moiety into the target cells.

Described herein are methods and vectors for rational, multiplexed manipulation of chromosomes within open reading frames (e.g., in protein libraries) or any segment of a chromosome in a cell or population of cells, in which various CRISPR systems are used.

This invention relates to a novel screening method that identifies simple molecular markers that are predictive of whether a particular disease condition is responsive to a specific treatment. Also, a method of diagnosing the susceptibility of an individual suffering from a disease to treatment with an HDAC inhibitor is provided. Also provided is a method of treating a proliferative disease or a condition which involves a change in cell differentiation or growth rate in a patient.

Compositions and methods are provided for forming a single RNA polynucleotide from a plurality of DNA oligonucleotides in a single reaction chamber using combined reagents in a single step reaction. DNA polymerase, RNA polymerase and single stranded (ss) DNA oligonucleotides are combined where each DNA oligonucleotide has one or more sequence modules, wherein one sequence module in the first ss DNA oligonucleotide is complementary to a sequence module at the 3′ end of the second ss DNA oligonucleotide; and wherein a second module on the first ss DNA oligonucleotide is an RNA polymerase promoter sequence; and forming a single RNA polynucleotide, excluding the RNA promoter sequence, derived from the first and second DNA oligonucleotides.

The present invention relates to novel methods for discovering traits and generating cellular systems having improved phenotypes. In particular, the present invention provides methods for the development of plants having agronomically optimized phenotypes by using targeted mutagenesis with few or no off-target effects. Targeted mutagenesis is achieved by the introduction of a base editor complex or of a STEME complex comprising an array of guide RNAs targeting a nucleic acid sequence of interest. The present invention also relates to cellular systems obtained by the methods described herein and to the use of a base editor complex or the STEME complex comprising an array of guide RNAs for generating a cellular system having an agronomically important phenotype and for identification of an agronomically important phenotype.