Provided herein are analogs of unnatural nucleotides bearing predominantly hydrophobic nucleobase analogs that form unnatural base pairs during DNA polymerase-mediated replication of DNA or RNA polymerase-mediated transcription of RNA. In this manner, the unnatural nucleobases can be introduced in a site-specific way into oligonucleotides (single or double stranded DNA or RNA), where they can provide for site-specific cleavage, or can provide a reactive linker than can undergo functionalization with a cargo-bearing reagent by means of reaction with a primary amino group or by means of click chemistry with an alkyne group of the unnatural nucleobase linker.

Provided herein are analogs of unnatural nucleotides bearing predominantly hydrophobic nucleobase analogs that form unnatural base pairs during DNA polymerase-mediated replication of DNA or RNA polymerase-mediated transcription of RNA. In this manner, the unnatural nucleobases can be introduced in a site-specific way into oligonucleotides (single or double stranded DNA or RNA), where they can provide for site-specific cleavage, or can provide a reactive linker than can undergo functionalization with a cargo-bearing reagent by means of reaction with a primary amino group or by means of click chemistry with an alkyne group of the unnatural nucleobase linker.

Provided herein are analogs of unnatural nucleotides bearing predominantly hydrophobic nucleobase analogs that form unnatural base pairs during DNA polymerase-mediated replication of DNA or RNA polymerase-mediated transcription of RNA. In this manner, the unnatural nucleobases can be introduced in a site-specific way into oligonucleotides (single or double stranded DNA or RNA), where they can provide for site-specific cleavage, or can provide a reactive linker than can undergo functionalization with a cargo-bearing reagent by means of reaction with a primary amino group or by means of click chemistry with an alkyne group of the unnatural nucleobase linker.

The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA-targeting systems comprising a novel DNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA. Methods for making and using and uses of such systems, methods, and compositions and products from such methods and uses are also disclosed and claimed.

The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA-targeting systems comprising a novel DNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA. Methods for making and using and uses of such systems, methods, and compositions and products from such methods and uses are also disclosed and claimed.

The present disclosure provides multiplexed methods, and constructs made to be used in said methods, for characterizing microbes from a biological sample to both rapidly identify the microbe and characterize drug susceptibility or resistance and perform microbial taxa identification and nucleic acid target detection at high multiplexity. The methods can also be used to predict future microbe drug susceptibility or resistance.

The present disclosure provides multiplexed methods, and constructs made to be used in said methods, for characterizing microbes from a biological sample to both rapidly identify the microbe and characterize drug susceptibility or resistance and perform microbial taxa identification and nucleic acid target detection at high multiplexity. The methods can also be used to predict future microbe drug susceptibility or resistance.

This disclosure provides, among other things, a reagent system for nucleic acid analysis. In some embodiments, the system may comprise a plurality of oligonucleotide sets each set comprising at least (a) a competitor oligonucleotide that hybridizes to a target sequence and varies in concentration from mixture to mixture and (b) a detector oligonucleotide that also hybridizes to the target sequence and contains a barcode that indicates the concentration of the competitor oligonucleotide in the oligonucleotide set. The reagent system may be used to analyze a nucleic acid sample.

This disclosure provides, among other things, a reagent system for nucleic acid analysis. In some embodiments, the system may comprise a plurality of oligonucleotide sets each set comprising at least (a) a competitor oligonucleotide that hybridizes to a target sequence and varies in concentration from mixture to mixture and (b) a detector oligonucleotide that also hybridizes to the target sequence and contains a barcode that indicates the concentration of the competitor oligonucleotide in the oligonucleotide set. The reagent system may be used to analyze a nucleic acid sample.

The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA-targeting systems comprising a novel DNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA. Methods for making and using and uses of such systems, methods, and compositions and products from such methods and uses are also disclosed and claimed.