The present invention relates to genetically modified bacteria and methods of optimizing genetically modified bacteria for the production of a metabolite.

Provided herein are methods of identifying a cell uptake modulator of a molecule that include (a) contacting a plurality of cells of a cell-containing biological sample with a plurality of gene-editing agents, wherein a gene-editing agent from the plurality of gene-editing agents recognizes and alters a target gene of at least one cell of the plurality of cells; (b) contacting the plurality of cells with a plurality of molecules, wherein at least one molecule of the plurality of molecules is transported into at least one cell of the plurality of cells; and (c) detecting a presence of the at least one molecule in the plurality of cells, thereby identifying the cell uptake modulator of the molecule.

The invention encompasses compositions, kits and methods for modifying bacteria, preferably naturally occurring bacteria, in situ. These can be used to treat, prevent or cure microbiome-associated diseases or disorders by modulating the molecules expressed and/or secreted by bacterial populations of the microbiome in a specific manner. The genomic modifications can modify the interactions between part or all of these populations and the host in a way that decreases their deleterious potential on host health. The compositions, kits and methods of the invention do not result in the direct death of these populations or a direct significant inhibition of their growth. The invention further includes methods for screening for genetic modifications in the bacteria, for determining the efficiency of vectors at inducing these genetic mutations, and for determining the effects of these mutations on bacterial growth.

Embodiments herein describe systems and methods to identify genetic silencers. Many embodiments screen one or more DNA fragments to identify sequences that are capable of silencing gene expression. Once identified, silencer elements can be utilized for many applications, including precision medicine.

Embodiments herein describe systems and methods to identify genetic silencers. Many embodiments screen one or more DNA fragments to identify sequences that are capable of silencing gene expression. Once identified, silencer elements can be utilized for many applications, including precision medicine.

Provided herein are methods and composition for trackable genetic variant libraries. Further provided herein are methods and compositions for recursive engineering. Further provided herein are methods and compositions for multiplex engineering. Further provided herein are methods and compositions for enriching for editing and trackable engineered sequences and cells using nucleic acid-guided nucleases.

The application relates to a deep scanning mutagenesis library to interrogate phenotypic changes in a population of cells comprising a plurality of CRISPR-Cas system guide RNAs targeting genomic sequences within at least one continuous genomic region, wherein the guide RNAs target at least 100 genomic sequences upstream of a PAM sequence for every 1000 base pairs within the continuous genomic region and methods for their use.

The present disclosure provides recombinant host cells comprising a pathway capable of producing a cannabinoid and a nucleic acid derived from a Cannabis trichome mRNA that that does not encode an enzyme in the pathway but enhances the host cells' ability to produce the cannabinoid. The disclosure also provides methods of using host cells to produce cannabinoids.

The present disclosure relates generally to detection of long noncoding RNA (lncRNA) molecules in a sample or diagnosis of subject based upon detection of long noncoding RNAs in a sample, specifically to identify and use of molecular biomarkers or cancer including malignant glioma. Also provided are compositions and methods for treating malignant glioma in a subject, as well as human brain organoid models of malignant glioma and methods of generating and using the same.

The present invention relates to systems and methods for screening natural products such as secondary metabolites produced by engineered microbial strains.