Abstract: The present disclosure provides codon optimized Factor VIII sequences, vectors, and host cells comprising codon optimized Factor VIII sequences, polypeptides encoded by codon optimized Factor VIII sequences, and methods of producing such polypeptides.

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: We have identified panels of proxy single nucleotide polymorphisms (SNPs) that are highly predictive of particular HLA risk alleles, and concordant across multi-ethnic populations. Accordingly, methods are provided involving clinical DNA testing for HLA panel markers to assess risk for life-threatening adverse drug reactions associated with the human leucocyte antigen (HLA) alleles HLA-B*57:01, HLA-B*15:02, HLA-A*31:01 and HLA-B*58:01. Methods of treating a subject with a drug associated with an adverse drug reaction (ADR) are provided. Based on the assessed risk to a subject for developing an adverse drug reaction in response to a drug, appropriate administrations of the drug can be made. In some embodiments of the method, the drug is administered when there is a low assessed risk of ADR in the subject. Alternatively, when there is a high assessed risk of ADR in the subject, a reduced dosage of the drug, or no drug, can be administered.

Abstract: We have identified panels of proxy single nucleotide polymorphisms (SNPs) that are highly predictive of particular HLA risk alleles, and concordant across multi-ethnic populations. Accordingly, methods are provided involving clinical DNA testing for HLA panel markers to assess risk for life-threatening adverse drug reactions associated with the human leucocyte antigen (HLA) alleles HLA-B*57:01, HLA-B*15:02, HLA-A*31:01 and HLA-B*58:01. Methods of treating a subject with a drug associated with an adverse drug reaction (ADR) are provided. Based on the assessed risk to a subject for developing an adverse drug reaction in response to a drug, appropriate administrations of the drug can be made. In some embodiments of the method, the drug is administered when there is a low assessed risk of ADR in the subject. Alternatively, when there is a high assessed risk of ADR in the subject, a reduced dosage of the drug, or no drug, can be administered.

Abstract: We have identified panels of proxy single nucleotide polymorphisms (SNPs) that are highly predictive of particular HLA risk alleles, and concordant across multi-ethnic populations. Accordingly, methods are provided involving clinical DNA testing for HLA panel markers to assess risk for life-threatening adverse drug reactions associated with the human leucocyte antigen (HLA) alleles HLA-B*57:01, HLA-B*15:02, HLA-A*31:01 and HLA-B*58:01. Methods of treating a subject with a drug associated with an adverse drug reaction (ADR) are provided. Based on the assessed risk to a subject for developing an adverse drug reaction in response to a drug, appropriate administrations of the drug can be made. In some embodiments of the method, the drug is administered when there is a low assessed risk of ADR in the subject. Alternatively, when there is a high assessed risk of ADR in the subject, a reduced dosage of the drug, or no drug, can be administered.

Abstract: Methods and compositions for use in engineering cells to secrete therapeutic biomolecules into the blood stream in vivo in response to an individual's personal biological needs.

Abstract: The invention features compositions and methods for altering mutations associated with Rett Syndrome (RTT). Provided herein are compositions and methods of using base editors comprising a polynucleotide programmable nucleotide binding domain and a nucleobase editing domain in conjunction with a guide polynucleotide. Also provided herein are base editor systems for editing nucleobases of target nucleotide sequences.

Abstract: The invention relates to logic-gate-based Type II or Type V CRISPR-Cas constructs and methods for modifying gene expression using the CRISPR-Cas constructs and CRISPR-Cas effector proteins.

Abstract: In one aspect, embodiments disclosed herein are directed to engineered CRISPR-Cas effector proteins that comprise at least one modification compared to an unmodified CRISPR-Cas effector protein that enhances binding of the of the CRISPR complex to the binding site and/or alters editing preference as compared to wild type. In certain example embodiments, the CRISPR-Cas effector proteins a Type II effector protein. In certain other example embodiments, the Type V effector protein is Cas9 or an orthologs or engineered variant thereof. Example Cas9 proteins suitable for use in the embodiments disclosed herein are discussed in further detail below.

Abstract: Provided is a method for modulating RNA splicing by inducing a base mutation at a splice site or a base substitution in a polypyrimidine region. The method comprises expressing a targeting cytosine deaminase in a cell, to induce AG at a 3? splice site of an intron of interest in a gene of interest to mutate into AA, or to induce GT at a 5? splice site of the intron of interest in a gene of interest to mutate to AT, or to induce a plurality of Cs in a polypyrimidine region of the intron of interest in a gene of interest to respectively mutate into Ts. The method specifically blocks an exon recognition process, modulates a selective splicing process of endogenous mRNA, induces exon skipping, activates an alternative splice site, induces mutually exclusive exon conversion, induces intron retention, and enhances an exon.

Abstract: The present invention provides polynucleotide vectors for high expression of heterologous genes. Some vectors further comprise novel transposons and transposases that further improve expression. Further disclosed are vectors that can be used in a gene transfer system for stably introducing nucleic acids into the DNA of a cell. The gene transfer systems can be used in methods, for example, gene expression, bioprocessing, gene therapy, insertional mutagenesis, or gene discovery.

Abstract: In accordance with the purpose(s) of the present disclosure, as embodied and broadly described herein, the disclosure, in one aspect, relates to methods for modifying cells such as, for example, changing shape, cell force, and/or modifying structural integrity of the cells. In a further aspect, the disclosure relates to controlling membrane permeability in cells by applying an electric current, where the cells are in contact with a polymeric nanofiber array and wherein direction and voltage of the electric current can be modified to induce the desired cellular response. In some aspects, the method results in higher survivability for cells during electroporation, greater permeability to molecules and/or drugs of different sizes, and greater transfection efficiencies for rare primary cells.

Abstract: Provided is a method of preparing a circular permutation (CP)-based functional recombinant human-derived fibroblast growth factor 7 and a use thereof. The fibroblast growth factor 7 to which a circular permutation is applied (CP-hFGF7115-114) is independently expressed in a host cell, such that soluble overexpression of the fibroblast growth factor 7 may be induced without causing problems according to the related art, such as lower expression level and stability compared to those of a wild-type hFGF7 protein and amino acid changes in a process of removing a fusion tag.

Abstract: This disclosure relates to isolated oligonucleotides comprising duplex regions targeting human CFB mRNA, and delivery systems, and compositions comprising the same, and methods of using the same for inhibiting or downregulating CFB gene expression.

Abstract: The present invention is related to the field of therapeutic delivery platforms. Such therapeutic delivery platforms are based upon the formation of proteinacous exovesicles that bind nucleic acid payloads (e.g., mRNA, siRNA, shRNA etc.). These nucleic acid payloads may hind to the proteinacous vesicle either directly or as an adduct of a linker molecule. As one example, the linker molecule may be an arc 3?UTR that is bound to an Arc protein exovesicle.

Abstract: The present invention provides a method of modifying a targeted site of a double-stranded DNA, comprising a step of introducing a complex wherein a nucleic acid sequence-recognizing module that specifically binds to a target nucleotide sequence in a double-stranded DNA and PmCDA1 are bonded, into a cell containing the double-stranded DNA, and culturing the cell at a low temperature at least temporarily to convert the targeted site, i.e., the target nucleotide sequence and nucleotides in the vicinity thereof, to other nucleotides, or delete the targeted site, or insert nucleotide into the site.

Abstract: The present invention pertains to a pharmaceutical composition for preventing or treating squamous cell carcinoma, the pharmaceutical composition containing a highly expressed lncRNAs in esophageal squamous cell carcinoma (HERES) expression inhibitor. More specifically, the present invention pertains to a pharmaceutical composition which uses a HERES expression inhibitor to reduce the expression of HERES and affect Wnt signaling pathways, and thereby prevent or treat squamous cell carcinoma. The present inventors discovered that the expression pattern of HERES is related to the onset of squamous cell carcinoma, and found that HERES can be a target for treating squamous cell carcinoma.

Abstract: A method for carrying out a process for an amplification of nucleic acids with sample nucleic acids and reference nucleic acids being amplified in separate reaction batches. Signals of the amplification are observed in real time. A number of amplification cycles and/or a duration of the amplification process are dynamically adjusted depending on the observed signals of the amplification.

Abstract: The present invention relates to a nucleic acid nanostructure comprising at least one scaffold strand and a plurality of staple strands, wherein said nanostructure, preferably said at least one scaffold strand, comprises at least one nucleic acid sequence encoding a gene. The present invention further relates to a composition comprising a nucleic acid nanostructure, and to a collection of nucleic acid sequences or collection of plasmids encoding a nucleic acid nanostructure. Furthermore, the present invention relates to a nucleic acid nanostructure or composition comprising a nucleic acid nanostructure for use in medicine; preferably for use in a method of preventing, treating and/or diagnosing a disease or disorder. The present invention also relates to a method of expressing a gene from a nucleic acid nanostructure, and to a use of a nanostructure or of a composition for gene expression.

Abstract: A combined system comprising two separate components, wherein the first component is a tag-exchange donor vector (TEDV) encoding a first cell surface tag (CST) exon flanked by a 3? intron fragment, and a gene of interest (GOI) in the antisense orientation, and the second component is an engineered cell containing within its genome a tag-exchange receiver site (TERS), encoding a second CST exon adjoined by a full intron sequence to an exon encoding a transmembrane domain, and also encoding a reporter gene in the antisense orientation, wherein paired recombinase mediated cassette exchange (RMCE) elements are included in the TEDV and TERS such that execution of RMCE between the TEDV and TERS results in exchange of the reporter element for the GOI encoded by the TEDV, and exchange of the first CST exon for the second CST exon, such that the derivative engineered cell now expresses the first CST and GOI, in place of the second CST and the reporter gene.