Abstract: A Method of generating binding peptide sequences to a target sequence, the method comprising: Receiving, using a processor configured by code executing therein, a data object corresponding to a protein target; Searching, using the data object, a protein interaction database for at least one partner protein to the target protein; Identifying at least one partner protein to the target protein; Providing the at least one partner protein to a computational model configured to output a predicted protein sequence predicted to interact with the target sequence; and Identifying at least one subsequence within the predicted protein sequence that meets a predetermined interaction threshold.

Abstract: Provided herein are methods and compositions for differentiating induced pluripotent stem cells into granulosa-like cells by overexpressing transcription factors such as NR5A1 and a RUNX family protein (e.g., RUNXI and/or RUNX2).

Abstract: Provided herein are methods and compositions for differentiating induced pluripotent stem cells into granulosa-like cells by overexpressing transcription factors such as NR5A1 and a RUNX family protein (e.g., RUNX1 and/or RUNX2).

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: 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], or [SEQ ID No. 6]. The ubiquitin ligase recruiting domain recruits an E3 ubiquitin ligase, which may be CHIP?R [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 system and method of using contrastive language-image pre-training (CLIP) to devise a unified, sequence-based framework to design target-specific peptides via contrastive learning. In one or more further implementations, using known experimental binding proteins as scaffolds, a method is provided to generate a streamlined inference pipeline that efficiently selects peptides for downstream screening. In a further implementation, one or more compounds that are fused candidate peptides to E3 ubiquitin ligase domains that exhibit robust intracellular degradation of pathogenic protein targets in human cells.

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: Provided herein are methods and compositions for differentiating induced pluripotent stem cells into primordial germ cell-like cells by overexpressing transcription factors such as DLX5, HHEX, and/or FIGLA.

Abstract: Provided herein are methods and compositions for differentiating induced pluripotent stem cells into oogonia-like cells by overexpressing transcription factors such as ZNF281, LHX8, and/or SOHLH1.

Abstract: Provided herein are methods and compositions for differentiating induced pluripotent stem cells into granulosa-like cells by overexpressing transcription factors such as NR5A1 and a RUNX family protein (e.g., RUNX1 and/or RUNX2).

Abstract: An isolated chimeric molecule is provided comprising: (i) a degradation domain comprising an E3 ubiquitin ligase motif without lysine residues; (ii) a targeting domain comprising a substrate-binding motif which is heterologous to the E3 ubiquitin ligase motif and configured to bind to Beta-Catenin; and (iii) a linker coupling said degradation domain to said targeting domain.

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: 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: In one or more aspects, the inventions described herein are directed to chimeric molecules and methods of making the same that provide improved protein modulating processes including, but not limited to, ubiquitination/deubiquination, lipidation/delipidation, SUMOylation/deSUMOylation, nitrosylation/denitrosylation, phosphporylation/dephosphorylation, acetylation/deacetylation, alkylation/dealklyation, methylation/demethylation, carboxylaton/decarboxylation, glycoysylation/deglycoylation, hydroxylation/dehydroxylation, and disulfide bond formation and breakage. In particular, the present disclose provides chimeric molecules including (i) a post-translational modifications (PTMs) domain and (ii) a targeting domain comprising a substrate-binding motif which is heterologous to the PTMS domain, and (iii) a linker that couples the PTMS domain to the targeting domain.

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: 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: Described herein are compositions and methods for generating a viable cell that expresses at least one or more woolly mammoth genes. Also described herein are compositions and methods for generating an embryo, blastula, oocyte, or non-human organism that expresses one or more woolly mammoth genes.

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: 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: 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.