Abstract: The present disclosure provides for systems, methods, and compositions for targeting and editing nucleic acids. In particular, the present disclosure provides non-naturally occurring or engineered RNA-targeting systems comprising a RNA-targeting Cas13 protein, at least one guide molecule, and at least one adenosine deaminase protein or catalytic domain thereof.

Abstract: The present disclosure provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides mutated Cas13 proteins and their use in modifying target sequences as well as mutated Cas13 nucleic acid sequences and vectors encoding mutated Cas13 proteins and vector systems or CRISPR-Cas13 systems.

Abstract: The embodiments disclosed herein utilized RNA targeting effectors to provide a robust CRISPR-based diagnostic with attomolar sensitivity. Embodiments disclosed herein can detect broth DNA and RNA with comparable levels of sensitivity and can differentiate targets from non-targets based on single base pair differences. Moreover, the embodiments disclosed herein can be prepared in freeze-dried format for convenient distribution and point-of-care (POC) applications. Such embodiments are useful in multiple scenarios in human health including, for example, viral detection, bacterial strain typing, sensitive genotyping, and detection of disease-associated cell free DNA.

Abstract: The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered RNA-targeting systems comprising a novel RNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA.

Abstract: An initial protein sequence is identified and varied to generate a plurality of variants. An activity of the plurality of protein sequences is measured quantitatively. Each of the plurality of protein sequences is provided as an input to a large language model (LLM) to generate a corresponding plurality of embeddings in a latent space. A subset of the plurality of embeddings is used to train a top layer model. The plurality of embeddings are provided as inputs to the top layer model to generate outputs representing predictions of the activity of the plurality of protein sequences. A subset of the plurality of protein sequences is selected based on the top layer model outputs. The method repeats, with the selected subset of the plurality of protein sequences playing the role of the initial protein sequence in the initial iteration, until some termination criterion is satisfied.

Abstract: Provided herein are methods and systems for detecting a target nucleic acid sequence. The method comprises contacting an oligonucleotide comprising the target nucleic acid sequence with a transposon complex; inserting one or more T7 RNA promoters into the oligonucleotide using the transposase; and (c) amplifying the target nucleic acid sequence. The transposon complex may comprise a transposase and a transposon sequence comprising one or more T7 RNA promoters. The target nucleic sequence may be amplified by generating RNA oligonucleotides comprising the target nucleic acid sequence via transcription from the inserted one or more T7 RNA promoters. The amplified target nucleic acid may be detected using a CRISPR Cas13-based detection system.

Abstract: Systems and methods for rapid diagnostics related to the use of CRISPR effector systems and optimized guide sequences for detection of coronavirus, including multiplex lateral flow diagnostic devices and methods of use, are provided.

Abstract: The present invention generally relates to plants comprising a CRISPR system or parts of a CRISPR system, compositions, containers, polynucleotide, vectors, delivery systems, parts of plants, methods for production, CRISPR systems, and components thereof. Further aspects of the invention include a method for identifying a CRISPR system which is functional in a plant cell and a method for improving a CRISPR system in a plant.

Abstract: The invention provides for systems, methods, and compositions for targeting and editing nucleic acids. In particular, the invention provides non-naturally occurring or engineered RNA-targeting systems comprising a RNA-targeting Cas13 protein, at least one guide molecule, and at least one adenosine deaminase protein or catalytic domain thereof.

Abstract: The invention relates to compositions and methods for RNA editing. In particular, ribozymes can be utilized to enhance RNA trans-splicing.

Abstract: Disclosed are compositions comprising a lipid nanoparticle and a modified biomolecular corona. In some embodiments, the modified biomolecular corona comprises a fused cell-specific binding domain. In some embodiments, the modified biomolecular corona protein has been additionally modified such that it does not bind substantially to its natural receptor. In some embodiments, the fused cell-specific binding domain binds to a target cell.

Abstract: The present disclosure provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides mutated Cas13 proteins and their use in modifying target sequences as well as mutated Cas13 nucleic acid sequences and vectors encoding mutated Cas13 proteins and vector systems or CRISPR-Cas13 systems.

Abstract: This disclosure provides systems, methods, and compositions for site-specific genetic engineering using Programmable Addition via Site-Specific Targeting Elements (PASTE). PASTE comprises the addition of an integration site into a target genome followed by the insertion of one or more genes of interest or one or more nucleic acid sequences of interest at the site. PASTE combines gene editing technologies and integrase technologies to achieve unidirectional incorporation of genes in a genome for the treatment of diseases and diagnosis of disease.

Abstract: The embodiments disclosed herein utilized RNA targeting effectors to provide a robust CRISPR-based diagnostic with attomolar sensitivity. Embodiments disclosed herein can detect broth DNA and RNA with comparable levels of sensitivity and can differentiate targets from non-targets based on single base pair differences. Moreover, the embodiments disclosed herein can be prepared in freeze-dried format for convenient distribution and point-of-care (POC) applications. Such embodiments are useful in multiple scenarios in human health including, for example, viral detection, bacterial strain typing, sensitive genotyping, and detection of disease-associated cell free DNA.

Abstract: The invention provides for systems, methods, and compositions for targeting and editing nucleic acids. In particular, the invention provides non-naturally occurring or engineered RNA-targeting systems comprising a RNA-targeting Cas13 protein, at least one guide molecule, and at least one adenosine deaminase protein or catalytic domain thereof.

Abstract: Provided herein is a nucleic acid detection system comprising: a CRISPR system comprising an effector protein and one or more guide RNAs designed to bind to corresponding target molecules; an RNA-based masking construct; and optionally, nucleic acid amplification reagents to amplify target RNA molecules in a sample. In another aspect, the embodiments provide a polypeptide detection system comprising: a CRISPR system comprising an effector protein and one or more guide RNAs designed to bind a trigger RNA, an RNA-based masking construct; and one or more detection aptamers comprising a masked RNA polymerase promoter binding site or a masked primer binding site. In some embodiments, the system may be used to detect viruses in samples.

Abstract: This disclosure provides systems, methods, and compositions for site-specific genetic engineering using Programmable Addition via Site-Specific Targeting Elements (PASTE). PASTE comprises the addition of an integration site into a target genome followed by the insertion of one or more genes of interest or one or more nucleic acid sequences of interest at the site. PASTE combines gene editing technologies and integrase technologies to achieve unidirectional incorporation of genes in a genome for the treatment of diseases and diagnosis of disease.

Abstract: The embodiments disclosed herein utilized RNA targeting effectors to provide a robust CRISPR-based diagnostic with attomolar sensitivity. Embodiments disclosed herein can detect both DNA and RNA with comparable levels of sensitivity and can differentiate targets from non-targets based on single base pair differences. Moreover, the embodiments disclosed herein can be prepared in freeze-dried format for convenient distribution and point-of-care (POC) applications. Such embodiments are useful in multiple scenarios in human health including, for example, viral detection, bacterial strain typing, sensitive genotyping, and detection of disease-associated cell free DNA.

Abstract: Systems and methods for rapid diagnostics related to the use of combinations of CRISPR effector systems with optimized guide sequences, OSD probes, RNA probes and/or RNase H for detection of nucleic acid sequences, such as sequences from coronavirus, as well as multiplex lateral flow diagnostic devices and methods of use, are provided.

Abstract: The invention relates to compositions and methods for targeting polynucleotides with eukaryotic RNA-guided nucleases. In particular, programmable RNA-guided DNA endonucleases termed Fanzors, can be harnessed for genome editing.