In other embodiments, the term "nucleotide analogs" refers to nucleotides having modified base moieties. The term "design" or "oligomer design" or "ASO Sequence" as used herein refers to a pattern of nucleotides (e.g., DNA) and nucleotide analogs (e.g., LNA) in a given sequence. In yet other embodiments, polynucleotides comprise a nucleotide sequence encoding a protein or polypeptide. In some embodiments, the oligomer is a single stranded molecule, and does not comprise short regions of, for example, at least 3, 4 or 5 contiguous nucleotides, which are complementary to equivalent regions within the same oligomer (i.e. duplexes)--in this regard, the oligomer is not (essentially) double stranded. The term "expression" as used herein refers to a process by which a polynucleotide produces a gene product, for example, a RNA or a polypeptide. The term "polynucleotide" as used herein refers to two or more nucleotides linked in sequence. It includes, without limitation, transcription of the polynucleotide into messenger RNA (mRNA) and the translation of an mRNA into a polypeptide.




Expression produces a "gene product." As used herein, a gene product can be either a nucleic acid, e.g., a messenger RNA produced by transcription of a gene, or a polypeptide which is translated from a transcript. The term "nucleic acids," "nucleotides," "nucleotide sequence," or "nucleic acid sequence" is intended to encompass plural nucleic acids (e.g., two or more, three or more, etc.). Gene products described herein further include nucleic acids with post transcriptional modifications, e.g., polyadenylation or splicing, or polypeptides with post translational modifications, e.g., methylation, glycosylation, the addition of lipids, association with other protein subunits, or proteolytic cleavage. In functional assays, IC50 is the concentration that reduces a biological response, e.g., transcription of mRNA or protein expression, by 50% of the biological response that is achieved without the therapeutic molecule. EC50 is the median effective concentration of a therapeutic molecule relative to a vehicle or saline control. IC50 is the median inhibitory concentration of a therapeutic molecule. An "effective amount" of a therapeutic molecule as disclosed herein is an amount sufficient to carry out a specifically stated purpose. An "effective amount" can be determined empirically and in a routine manner, in relation to the stated purpose. The term "nucleoside" as used herein is used to refer to a glycoside comprising a sugar moiety and a base moiety, and can therefore be used when referring to the nucleotide units, which are covalently linked by the internucleotide linkages between the nucleotides of the oligomer.



Likewise, particularly in the case of oligonucleotides where one or more of the internucleoside linkage groups are modified, the term "nucleotide" can refer to a "nucleoside" for example the term "nucleotide" can be used, even when specifying the presence or nature of the linkages between the nucleosides. In some embodiments, the terms "nucleotide", "unit" and "monomer" are used interchangeably. Non-limiting examples of the nucleotides having modified sugar moieties (e.g., LNA) are disclosed elsewhere herein, e.g., 2'-O-methyl, 2'-fluoro (2'-F), 2'-O-methoxyethyl (2'-MOE), and 2',4'-constrained 2'-O-ethyl (cEt). The nucleotides having modified base moieties include, but are not limited to, 5-methylcytosine, isocytosine, pseudoisocytosine, 5-bromouracil, 5-propynyluracil, 6-aminopurine, 2-aminopurine, inosine, diaminopurine, or 2-chloro-6-aminopurine. In certain embodiments when referring to the sequence score formula disclosed herein, the nucleotide analog of cytosine is 5-methyl cytosine. The term "nucleotide sequence" refers to a molecule comprising at least two nucleotides connected to each other. The term "nucleotide" as used herein, refers to a glycoside comprising a sugar moiety, a base moiety and a covalently linked group (linkage group), such as a phosphate or phosphorothioate internucleotide linkage group, and covers both naturally occurring nucleotides, such as DNA or RNA, free Private Sexcam and non-naturally occurring nucleotides comprising modified sugar and/or base moieties, which are also referred to as "nucleotide analogs" herein.



It will be recognized that when referring to a sequence of nucleotides or monomers, what is referred to is the sequence of bases, such as A, free private sexcam T, G, C or U, and analogs thereof. In some embodiments, polynucleotides comprise a nucleotide sequence longer than 10 nucleotides, 11 nucleotides, 12 nucleotides, 13 nucleotides, 14 nucleotides, 15 nucleotides, 16 nucleotides, 17 nucleotides, 18 nucleotides, 19 nucleotides, 20 nucleotides, 21 nucleotides, 22 nucleotides, 23 nucleotides, 24 nucleotides 26 nucleotides, 27 nucleotides, 28 nucleotides, 29 nucleotides, 30 nucleotides. In still other embodiments, polynucleotides comprise a nucleotide sequence longer than 100 nucleotides, longer than 200 nucleotides, longer than 300 nucleotides, longer than 400 nucleotides, longer than 500 nucleotides, longer than 1000 nucleotides, longer than 1500 nucleotides, longer than 2000 nucleotides, longer than 3000 nucleotides, longer than 4000 nucleotides, or longer than 5000 nucleotides. The server with the long list of anti-fascist activists posted by a user to encourage doxing, for example, is still active, and the list is still on Discord.



Therefore, for example, the complement of a sequence of 5' "ATGC"3' can be written as 3' "TACG"5' or 5' "GCAT"3'. The naked minds have many things to hide from the society; therefore, they click on these websites secretly at night. To help with her _9,000-a-year student debt, Jasmine, from Worcester, works as a cam girl and an exotic dancer - and she tells Sun Online in an exclusive interview that she can rake in up to _1000 a night. One is Alice, a casual jeans-and-hoodies kind of girl who is close with her brother and mom, and who is semi-secretly making a good living as a cam girl. By "toxic side effect" is meant an effect that causes debilitation of a living subject, including, but not limited to, death, pain, tremors, convulsions, seizures, an inhibition of movement, or loss of memory. Mammalian subjects include humans, domestic animals, farm animals, sports animals, and zoo animals including, e.g., humans, non-human primates, dogs, cats, guinea pigs, rabbits, rats, mice, horses, cattle, bears, and so on.