A log of molecular events experienced by a cell and timing indicators for those events are stored in existing polynucleotides through a process of creating a double strand break (“DSB”) in a polynucleotide and inserting a new polynucleotide sequence by repairing the DSB with homology directed repair (“HDR”). The presence, order, and number of new polynucleotide sequences provides a log of events and timing of those events. Cellular mechanisms for creating the DSB and/or repairing with HDR are regulated by intra- or extra-cellular signals. When the log is created in the DNA of a cell, the changes may be heritably passed to subsequent generations of the cell. A correlation between the cellular signals and sequence of inserted HDR templates allows for identification of events and the timing experienced by the cell.

The invention involves inducing 3-50 or more mutations (e.g., any whole number between 3 and 50 of mutations, with it noted that in some embodiments there can be up to 16 different RNA(s), e.g., sgRNAs each having its own a promoter, in a vector, such as AAV, and that when each sgRNA does not have its own promoter, there can be twice to thrice that amount of different RNA(s), e.g., sgRNAs, e.g., 32 or even 48 different guides delivered by one vector) in transgenic Cas9 eukaryotes to model genetic disease, e.g. cancer. The invention comprehends testing putative treatments with such models, e.g., testing putative chemical compounds that may be pharmaceutically relevant for treatment or gene therapy that may be relevant for treatment, or combinations thereof. The invention allows for the study of genetic diseases and putative treatments to better understand and alleviate a genetic disease or a condition, e.g., cancer.

The present disclosure provides oligomeric compounds. The present disclosure provides metabolically stable linkers that do not rapidly degrade in vivo. In certain embodiments, the present disclosure provides metabolically stable linkers for use in attaching a conjugate group to an oligonucleotide.

The present invention relates to the field of molecular biology and cell biology. More specifically, the present invention relates to a CRISPR-CAS system for a yeast host cell.

Disclosed are methods of treating cancer of the intraperitoneal cavity using compositions comprising nanoparticles without targeting agents. In addition, nanoparticles are described that comprise a highly toxic anticancer agent (e.g., an anticancer agent having an IC.sub.50 less than 1 nM) covalently bound via a linker to a triblock copolymer. Other nanoparticles that comprise Pt(IV) and an anticancer agent are also described. Also disclosed are nanoparticles comprising imaging agents non-covalently associated with a polymer, and methods of imaging cancer of the intraperitoneal cavity using compositions comprising nanoparticles without targeting agents.

A gene LBA5 for regulating lateral shoot angles, growth habits, and a plant architecture of Arachis hypogaea L., and use thereof are provided. In the present disclosure, a major gene LBA5 for controlling lateral shoot angles, growth habits, and a plant architecture of Arachis hypogaea L. is mapped and cloned from Arachis hypogaea L., which includes two homologous genes LBA5b and LBA5a and promoters thereof. The allelic variations of the gene can be selected through crossbreeding and backcrossing to achieve the genetic improvement on an angle between an Arachis hypogaea L. lateral shoot and a main stem. Through a genetic engineering operation for the gene and a change for a promoter sequence of the gene, the function or expression level of this gene in a procumbent Arachis hypogaea L. variety can be adjusted to further regulate an angle between an Arachis hypogaea L. lateral shoot and a main stem.

Disclosed are methods for treating Set1/COMPASS-associated cancers characterized by expression of Set1B/COMPASS. The methods typically include administering a therapeutic amount of an inhibitor of the Set1B/COMPASS pathway and/or an agonist for a target that is negatively regulated by the Set1B/COMPASS pathway.

Provided herein are engineered red blood cells expressing rare blood antigen group profiles, and methods of making use the same, are described. Also provided are recombinant reagent red blood cells that express or lack the expression of at least one protein (e.g., a blood group antigen) on its surface and uses thereof.

Disclosed herein are methods and compositions for inactivating mutant genes associated with LCA, using engineered nucleases comprising a DNA binding domain and a cleavage domain or cleavage half-domain in conditions promoting the cleavage of the mutant genes. Polynucleotides encoding nucleases, vectors comprising polynucleotides encoding nucleases, and cells comprising polynucleotides encoding nucleases and/or cells comprising nucleases are also provided.

The present disclosure provides methods and systems for identification of genomic regions for therapeutic targeting. A method for identifying one or more genomic regions for therapeutic targeting, which may facilitate re-programming of a cell from one phenotypic state to another, may comprise: providing single-cell RNA-seq data for a plurality of diseased cells and a plurality of normal cells of a cell type; mapping the single-cell RNA-seq data for the plurality of diseased cells and the plurality of normal cells into a latent space corresponding to a plurality of phenotypic states of the cell type; identifying, based at least in part on a topology of the latent space, the one or more genomic regions for therapeutic targeting; and electronically outputting the one or more genomic regions for therapeutic targeting.