Abstract: An oral care antimicrobial composition comprises about 0.1 to about 99.9 wt. % of at least one compound having the structure of Also disclosed is a process for preparing the composition and methods of use thereof.

Abstract: Peptide-E3 ubiquitin ligase fusions representing minimal protein to proteasome linkers are specifically targeted to degrade endogenous FOXP3 proteins in regulatory T cells. An engineered peptide for functional inactivation of a target regulatory T cell includes a fusion protein comprising a targeting domain and a ubiquitin ligase recruiting domain, wherein the targeting domain is engineered to bind FOXP3 of the target regulatory T cell for mediated degradation by the ubiquitin-proteosome pathway. The targeting domain may comprise a peptide having amino acid [SEQ ID No. 3], [SEQ ID No. 4], [SEQ ID No. 5], [SEQ ID No. 6], or [SEQ ID No. 7]. The ubiquitin ligase recruiting domain recruits an E3 ubiquitin ligase, which may be CHIP?TPR [SEQ ID No. 2]. An engineered minimal, specific, nucleotide-encodable, FOXP3 protein to proteasome linker comprises a peptide-E3 ubiquitin ligase fusion in which the peptide binds to FOXP3.

Abstract: A highly specific molecular diagnostic for the detection of an intended target protein within a matter of minutes employing a peptide beacon, the peptide beacon having a stem section having two ends attached to a fluorophore and a quencher and a loop section having a receptor sequence for binding with the intended target protein, the two ends forming a coiled-coil structure when the receptor sequence is unbound with the intended target protein and an open-coil structure when the receptor sequence is bound with the intended target protein, wherein the peptide beacons are able to provide a signal for the detection of the receptor binding domain of the intended target protein, such as SARS-CoV-2 spike protein, by the stem section transitioning from the coiled-coil structure to the open-coil structure that moves the fluorophore away from the quencher, resulting in an increase in the fluorescence yield of the peptide beacon.

Abstract: SpRYc is a grafted ScCas9++-SpRY chimeric Cas9 possessing minimal 5?-NNN-3? PAM specificity. SpRYc comprises the N-terminus (residues 1-1119) of ScCas9++ (Sc++), including the flexible loop, followed by the region of SpRY (residues 1111-1368) spanning its PAM-interacting domain mutations. Methods of altering gene expression include use of SpRYc in complex with guide RNA in a CRISPR-Cas9 system.

Abstract: Engineered Streptococcus canis Cas9 (ScCas9) variants include an ScCas9 protein with its PID being the PID amino acid composition of Streptococcus pyogenes Cas9 (SpCas9)-NG, an ScCas9 protein having a threonine-to-lysine substitution mutation at position 1227 in its amino acid sequence (Sc+), and an ScCas9 protein having a threonine-to-lysine substitution mutation at position 1227 and a substitution of residues ADKKLRKRSGKLATE [SEQ ID No. 4] in position 365-379 in the ScCas9 open reading frame (Sc++). Also included are CRISPR-associated DNA endonucleases with a PAM specificity of 5?-NG-3? or 5?-NNG-3? and a method of altering expression of a gene product by utilizing the engineered ScCas9 variants.

Abstract: A self-reconfiguring genome uses a cassette having operons or DNA sequences that code for guide RNA, reverse transcriptase, donor RNA, and a CRISPR cleavage enzyme. A self-reconfiguring genome may be based on lambda recombineering of in situ generated oligonucleotides. A method for programmable self-modification of a cellular genome includes transcribing guide RNA from a self-reconfiguring cassette, associating the transcribed guideRNA with the CRISPR enzyme, intercalating a region of complimentary sequence within an integration site of the genome, cutting upstream of a PAM site within the integration site; transcribing the donorRNA, translating donorRNA to double-stranded DNA, and recombining the double-stranded DNA via homologous recombination at the cut site of the integration site.

Abstract: A Streptococcus canis Cas9 (ScCas9) ortholog and its engineered variants, possessing novel PAM specificity, is an addition to the family of CRISPR-Cas9 systems. ScCas9 endonuclease is used in complex with guide RNA, consisting of identical non-target-specific sequence to that of the guide RNA SpCas9, for specific recognition and activity on a DNA target immediately upstream of either an “NNGT” or “NNNGT” PAM sequence. A novel DNA-interacting loop domain within ScCas9, and other Cas9 orthologs, such as those from Streptococcus gordonii and Streptococcus angionosis facilitates a divergent PAM sequence from the “NGG” PAM of SpCas9.

Abstract: An attention-based graph architecture that exploits MSA Transformer embeddings to directly produce models of three-dimensional folded structures from protein sequences includes a method and system for augmenting the protein sequence to obtain multiple sequence alignments, producing enriched individual and pairwise embeddings from the multiple sequence alignments using an MSA-Transformer, extracting relevant features and structure latent states from the enriched individual and pairwise embeddings for use by a downstream graph transformer, assigning individual and pairwise embeddings to nodes and edges, respectively, using the downstream graph transformer to operate on node representations through an attention-based mechanism that considers pairwise edge attributes to obtain final node encodings, and projecting the final node encodings to form the computer-modeled folded protein structure. An induced distogram of the computer-modeled folded protein structure may be computed.

Abstract: Engineered Streptococcus canis Cas9 (ScCas9) variants include an ScCas9 protein with its PID being the PID amino acid composition of Streptococcus pyogenes Cas9 (SpCas9)-NG, an ScCas9 protein having a threonine-to-lysine substitution mutation at position 1227 in its amino acid sequence (Sc+), and an ScCas9 protein having a threonine-to-lysine substitution mutation at position 1227 and a substitution of residues ADKKLRKRSGKLATE [SEQ ID No. 4] in position 365-379 in the ScCas9 open reading frame (Sc++). Also included are CRISPR-associated DNA endonucleases with a PAM specificity of 5?-NG-3? or 5?-NNG-3? and a method of altering expression of a gene product by utilizing the engineered ScCas9 variants.

Abstract: Applications of a Streptococcus Cas9 ortholog from Streptococcus macacae (Smac Cas9), possessing minimal adenine-rich PAM specificity, include an isolated Streptococcus macacae Cas9 protein or transgene expression thereof, a CRISPR-associated DNA endonuclease with PAM interacting domain amino acid sequences that are at least 80% identical to that of the isolated Streptococcus macacae Cas9 protein, and an isolated, engineered Streptococcus pyogenes Cas9 (Spy Cas9) protein with a PID as either the PID amino acid composition of the isolated Streptococcus macacae Cas9 (Smac Cas9) protein or of a CRISPR-associated DNA endonuclease with PID amino acid sequences that are at least 80% identical to that of the isolated Streptococcus macacae Cas9 protein. A method for altering expression of at least one gene product employs Streptococcus macacae Cas9 endonucleases in complex with guide RNA, for specific recognition and activity on a DNA target immediately upstream of either an “NAA” or “NA” or “NAAN” PAM sequence.

Abstract: The present invention relates to a cell based genomic Recorded Accumulative Memory (geRAM) system (also referred to herein as Genomically Encoded Memory (GEM)) for recoding data (i.e., changes in nucleic acid sequences in cellular DNA in response to physical and/or chemical signal(s)) from the cellular environment.

Abstract: In a method for generating an elongated nucleic acid molecule, a nucleic acid addition of a first nucleic acid molecule attached to a first 3? or 5? protecting group to a nucleic acid immobilized on a surface produces an intermediate-length immobilized nucleic acid. The first protecting group is dissociated from the first nucleic acid molecule. A second nucleic acid molecule that is attached to a second associated a 3? or 5? associated protecting group is added to the intermediate-length nucleic acid. The second associated protecting group is dissociated from the second nucleic acid molecule. A sequentially-extended elongated immobilized nucleic acid molecule having a desired sequence and length is produced by sequentially extending the intermediate-length immobilized nucleic acid by adding additional nucleic acid molecules with associated protecting groups to the intermediate-length nucleic acid and dissociating the associated protecting group after each addition.

Abstract: Methods and compositions relating to an engineered peptide capable of binding to an infectious biological molecule for inhibition by mediated degradation using the ubiquitin proteasome pathway. The engineered peptide includes a targeting domain and an ubiquitin ligase recruiting domain. The engineered peptide includes a targeting domain and an ubiquitin ligase. The targeting domain is computationally-derived from a known receptor for the infectious biological molecule. The engineered peptide is optimized for minimal size and minimum off-target effects.

Abstract: Methods and compositions relating to an engineered peptide capable of binding to a biological molecule for viral inhibition. The engineered peptide is computationally-derived from soluble angiotensin-converting enzyme 2 (sACE2), a known receptor for viral spike proteins. The engineered peptide is optimized for minimal size and off-target effects. The engineered sACE2 peptide variants are a suitable targeting domain for fusion proteins of various effects.

Abstract: A DNA canvas comprising a plurality of uniquely-coded polymer strands immobilized on a substrate can be used to provide a reference map comprising a set of reference association polymers having a dual-barcode generated by nondestructively associating spatially-adjacent polymers on the DNA canvas, encoding digital information on the DNA canvas to provide a patterned DNA canvas by disabling a pattern of selected plurality of polymers strands to provide a set of data association polymers having a single bar code that corresponds to a single bit in the bitmap. The digital information capable of being retrieved by sequencing the set of reference and data association polymers, computationally recovering spatial locations of each of the selected polymer strands that were disabled and recovering the bitmap encoded in the pattern of disabled polymer strands by comparison of the set of reference association polymer sequences to the set of data association polymer sequences.

Abstract: A chimeric DNA:RNA guide for very high accuracy Cas9 genome editing employs nucleotide-type substitutions in nucleic acid-guided endonucleases for enhanced specificity. The CRISPR-Cas9 gene editing system is manipulated to generate chimeric DNA:RNA guide strands to minimize the off-target cleavage events of the S. pyogenes Cas9 endonuclease. A DNA:RNA chimeric guide strand is sufficient to guide Cas9 to a specified target sequence for indel formation and minimize off-target cleavage events due to the specificity conferred by DNA-DNA interactions. Use of chimeric mismatch-evading lowered-thermostability guides (“melt-guides”) demonstrate that nucleotide-type substitutions in the spacer can reduce cleavage of sequences mismatched by as few as a single base pair. The chimeric mismatch-evading lowered-thermostability guides replace most gRNA spacer positions with DNA bases to suppress mismatched targets under Cas9's catalytic threshold.

Abstract: The invention provides compositions and methods for repeatable directed endonucleases (RDEs) and methods for repeatedly, and specifically cleaving DNA offset from the RDE's DNA recognition sequence on the target nucleic acid rather than within the DNA recognition sequence. Conservation of the recognition sequence of the target nucleic acid enables for re-localization of an RDE back to the DNA recognition sequence for further cleavage. The RDEs and methods of the invention are useful in applications including, but not limited to, recording data into a genome, timing the order of biochemical pathway events, efficient genome engineering and encoding lagged cellular death.

Abstract: A 3D object according to the invention comprises substrate layers infiltrated by a hardened material. The 3D object is fabricated by a method comprising the following steps: Position powder on all or part of a substrate layer. Repeat this step for the remaining substrate layers. Stack the substrate layers. Transform the powder into a substance that flows and subsequently hardens into the hardened material. The hardened material solidifies in a spatial pattern that infiltrates positive regions in the substrate layers and does not infiltrate negative regions in the substrate layers. In a preferred embodiment, the substrate is carbon fiber and excess substrate is removed by abrasion.

Abstract: A 3D object according to the invention comprises substrate layers infiltrated by a hardened material. The 3D object is fabricated by a method comprising the following steps: Position powder on all or part of a substrate layer. Repeat this step for the remaining substrate layers. Stack the substrate layers. Transform the powder into a substance that flows and subsequently hardens into the hardened material. The hardened material solidifies in a spatial pattern that infiltrates positive regions in the substrate layers and does not infiltrate negative regions in the substrate layers. In a preferred embodiment, the substrate is carbon fiber and excess substrate is removed by abrasion.

Abstract: Engineered Streptococcus canis Cas9 (ScCas9) variants include an ScCas9 protein with its PID being the PID amino acid composition of Streptococcus pyogenes Cas9 (SpCas9)-NG, an ScCas9 protein having a threonine-to-lysine substitution mutation at position 1227 in its amino acid sequence (Sc+), and an ScCas9 protein having a threonine-to-lysine substitution mutation at position 1227 and a substitution of residues ADKKLRKRSGKLATE in position 365-379 in the ScCas9 open reading frame (Sc++). Also included are CRISPR-associated DNA endonucleases with a PAM specificity of 5?-NG-3? or 5?-NNG-3? and a method of altering expression of a gene product by utilizing the engineered ScCas9 variants.