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The modified uracil or uridine can be replaced by a compound having a single unique structure or by a plurality of compounds having different structures e. In one embodiment, the oncology-related polypeptides, oncology-related primary constructs and oncology-related mmRNA can also contain sequences that encode protein cleavage sites so that the oncology-related polypeptides, oncology-related primary constructs and oncology-related mmRNA can be released from a carrier region or a fusion partner by treatment with a specific protease for said protein cleavage site. Various protecting groups may be used to control the reaction. In a further embodiment, the compositions are administered to a subject who is a patient. In one embodiment, LNP formulations described herein may comprise a polycationic composition.

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This feature may be. The polypeptide based molecules of the present invention may be characterized as having both an N-terminus terminated by an amino acid with a free amino group NH2 and a C-terminus terminated by an amino acid with a free carboxyl group COOH.

In such embodiments, nucleotide modifications may also be present in the translatable region. One such example involves the use of lipid encapsulation to enable the effective systemic delivery of polyplex plasmid DNA Heyes et al. The number of reactive groups on the modified saccharide can be controlled in a. Formulations with the different lipidoids, including, but not limited to penta[3- 1-laurylaminopropionyl ]-triethylenetetramine hydrochloride TETA-5LAP; aka 98N, see Murugaiah 40 al.

Details for these oncology-related polynucleotides, oncology-related primary constructs, and oncology-related mmRNA follow.

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Transfection experiments can be conducted in relevant cell lines at and protein production can be assayed by ELISA at 12 hr, 24 hr, 48 hr, 72 hr and day 7 post-transfection. As a non-limiting example, the polycationic composition may eutfctics selected from formula of US Patent Publication No. The modified nucleotides e.

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In another embodiment, the length is at least nucleotides, or greater than nucleotides. R 12a is H, optionally substituted alkyl, optionally substituted hydroxyalkyl, optionally substituted hydroxyalkenyl, optionally substituted hydroxyalkynyl, optionally substituted aminoalkyl, optionally substituted aminoalkenyl, or optionally substituted aminoalkynyl, optionally substituted carboxyalkyl e. These AU rich signatures are particularly prevalent in genes with high rates of turnover.

Where the loop is found in a polypeptide and only alters the direction of the backbone, it may comprise four or more amino acid euetctics. It is advantageous to correlate the level with one or more clinical phenotypes or with an assay for a human disease biomarker.

In certain embodiments, a polypeptide to be utilized in accordance with the invention includes 2, 3, 4, 5, 6, 7, 8, 9, ixpp, or more mutations eutectixs shown in any of the sequences provided or referenced herein. Degradeable polyesters include, but are not limited to, poly serine esterpoly L-lactide-co-L-lysinepoly 4-hydroxy-L-proline esterand combinations thereof.

The cap further assists the removal of 5′ proximal introns removal during mRNA splicing.

USA1 – Modified polynucleotides encoding granulysin – Google Patents

In particular embodiments, R 1 is optionally substituted alkyl, and R 2 is icp. In another non-limiting example, if the nucleotides in the region are GGGAGA the guanine bases may be substituted by at least 1, at least 2, at least 3 or at least 4 cytosine bases.

It is not required that a cosmetic primary construct contain both a 5′ and 3′ flanking region. As described herein “nucleoside” is defined as a compound containing a sugar molecule e. As used herein, a “unit dose” refers to a discrete amount of xip pharmaceutical composition comprising a predetermined amount of the active ingredient. In further embodiments, each of R 13a and R 13b is independently, Eutdctics or optionally substituted alkyl. Codon options for each amino acid are given in Table 1.

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In some embodiments, B is a nucleobase selected from the group consisting of cytosine, guanine, adenine, and uracil. Biodegradable polymers have been previously used to protect nucleic acids other than mmRNA from degradation and been shown to result in sustained release of payloads in vivo Rozema et al.

In one embodiment, the therapeutic nanoparticles of the present invention may be formulated to be cancer specific. Preferably, the polynucleotides are mRNA in a form suitable for direct introduction into a target cell host, which in turn synthesizes the encoded polypeptide.

The modification may comprise replacing at least one phosphodiester linkage with a phosphorothioate linkage.

These nucleobases can be modified or wholly replaced to provide oncology-related polynucleotides, primary constructs, or mmRNA molecules having enhanced properties, e. This method can be used to induce cell death in any desired cell and has particular usefulness in the treatment of cancer where cells escape natural apoptotic signals.

In another embodiment, an MD1 euetctics formulation may be used to effectively deliver oncology-related polynucleotide, primary construct, or mmRNA to hepatocytes in vivo.

Examples of tertiary folds include domains and regions formed due to aggregation or separation of energetic forces. Provided herein are methods for targeting pathogenic microorganisms, such as bacteria, yeast, protozoa, helminthes and the like, using modified mRNAs that encode cytostatic or cytotoxic polypeptides. The oncology-related primary constructs or oncology-related mmRNA of the present invention may be designed to encode oncology-related polypeptides of interest eutecitcs as oncology-related peptides and proteins.