In one embodiment, the nucleotide sequence for the present disclosure is DNA. Therefore, in various embodiments, the oligomer of the invention comprises both a polynucleotide region which typically consists of a contiguous sequence of nucleotides, and a further non-nucleotide region. When referring to the oligomer of the invention comprising a contiguous nucleotide sequence, the compound can comprise non-nucleotide components, such as a conjugate component. In one embodiment, random therapeutic molecules comprising nucleotide sequences (e.g., oligomers) targeting certain regions of pre-mRNA or mRNA encoding MAPT, BASP1, or APP are prepared to test their toxicities. The invention also provides for a conjugate comprising the oligomer according to the invention as herein described, and at least one non-nucleotide or non-polynucleotide moiety covalently attached to said oligomer. In the context the term "conjugate" is intended to indicate a heterogeneous molecule formed by the covalent or non-covalent attachment ("conjugation") of the oligomer as described herein to one or more non-nucleotide, or non-polynucleotide moieties.



Examples of non-nucleotide or non-polynucleotide moieties include macromolecular agents such as proteins, fatty acid chains, sugar residues, glycoproteins, polymers, or combinations thereof. Examples of configurations of a gapmer, blockmer, mixmer, headmer, tailmer, or Watch online porns totalmer that can be used with the oligomer of the invention are described in U.S. In certain embodiments, examples of the oligomers (i.e., antisense oligonucleotides) include, but are not limited to, the oligomers listed in FIGS. The oligomers can include any oligomer design, e.g., a pattern of nucleoside sugar modifications. A molecule for the disclosure can also comprise a polynucleotide (e.g., oligomers). In certain embodiments, the oligomers target a pre-mRNA or mRNA encoding brain acid soluble protein 1 (BASP1). In certain embodiments, the therapeutic molecules (e.g., oligomers) target a pre-mRNA encoding an amyloid precursor protein. In certain embodiments, the oligomers target microtubule-associated protein tau (MAPT). Natural variants of the MAPT gene product are known. In a pathologic state associated with disease, MAPT is also known as neurofibrillary tangle protein or paired helical filament-tau (PHF-tau).



Typically proteins can be antibodies for a target protein. Conservation of proteins with PEST sequences among different species supports their functional significance. PEST sequences typically occur in proteins with high turnover rates. In one embodiment, antagonists to cytokines that utilize an .beta. Cypriot doctor Sergios Sergiou, who was one of the first people to see the young woman in the moments after the incident, said he felt she was telling the truth, adding that she was so distraught she passed out. I was clearing out my wardrobes last night and blitzed threw the last disc in the process. This is a last desperate act by an industry that has been on the ropes for some time now. Unlike the others, Valenstein - now professor emeritus of psychology and neuroscience at the University of Michigan - was a member of Heath's own profession. Premature ejaculation has been relatively a man's problem every now and then.



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