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Further, provided are oncology-related polynucleotides, oncology-related primary constructs or oncology-related mmRNA which may contain an internal ribosome entry site IRES. In some embodiments, the nucleic acid is translatable. In another embodiment, the therapeutic nanoparticle may include a conjugation of at least one targeting ligand. Circles identify the atoms comprising the respective chemical regions. As described herein, the nucleic acids of the invention do not substantially induce an innate immune response of a cell into which the mRNA is introduced. The present disclosure provides for modified nucleosides and nucleotides. In one embodiment, the block copolymers described herein may be included in a polyion complex comprising a non-polymeric micelle and the block copolymer.

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Scheme 1 provides a general method for phosphorylation of nucleosides, including modified nucleosides. Furthermore, administration may be facilitated at least in part by the use of, or in combination with, a medical device, system or component such as an ex-vivo organ care system. In particular embodiments, R 12a is H. The modified mRNAs as described herein may be used to increase the viability or longevity of an organ or tissue explant, or portion thereof.

In another embodiment, the modified mRNA may be formulated in a lipid-polycation complex which may further include a neutral lipid such as, but not limited to, cholesterol or dioleoyl phosphatidylethanolamine DOPE. As a non-limiting example, T7 RNA polymerase variants may be evolved using the continuous directed evolution system set out by Uxp et al.

US and International Pub. Alternatively, delayed absorption of a parenterally administered drug form is. A “reference polypeptide sequence” may, e.

USB2 – Modified polynucleotides encoding granulysin – Google Patents

The oncology-related primary constructs or oncology-related mmRNA of the present invention may be designed to encode oncology-related polypeptides of interest such as oncology-related peptides and proteins. The multiple functionalities of bifunctional oncology-related polynucleotides may be encoded by the RNA the function may not manifest until the encoded product is translated or may be a property of the polynucleotide itself. Such mRNA may be effective as a vaccine when administered to a subject.

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These include substitutional, insertional, deletion and covalent variants and derivatives. The liposome may have a molar ratio of nitrogen atoms in the cationic lipid to the phosphates in the RNA N: Examples of typical non-viral mediated techniques include, but are not limited to, electroporation, calcium phosphate mediated transfer, nucleofection, sonoporation, heat shock, magnetofection, liposome mediated transfer, microinjection, microprojectile mediated transfer nanoparticlescationic polymer mediated transfer DEAE-dextran.

The substitutions may be single, where only one amino acid in the eutevtics has been substituted, or they may be multiple, where two ektectics more amino acids have been substituted in the same molecule. Loops may be open or closed. Exemplary syntheses of modified nucleotides, which are incorporated into a modified nucleic acid or mmRNA, e.

The oncology-related polynucleotide, primary construct, and mmRNA of the invention can be formulated using one or more liposomes, lipoplexes, or lipid nanoparticles.

Large polymeric nanoparticles nm nm in diameter which have been coated densely with a low molecular weight polyethylene glycol PEG diffused through mucus only 4 to 6-fold lower than the same particles diffusing in water Lai et al.

For example, oncology-related polypeptides of interest may belong to a family of proteins which are expressed in a particular cell, tissue or at some time during development.

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These molecules may also by convention be referred to as multi-functional. For example, the building block molecule, which may be incorporated into a polynucleotide, primary construct, or mmRNA, can be:.

WO and WO; each of which is herein incorporated by reference in its entirety. 400 of racemic mixtures can also be carried out by elution on a column packed with an optically active resolving agent e. In accordance with some embodiments, a method of administering pharmaceutical compositions comprising one or more proteins to be delivered to 400 subject in need thereof is provided.

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Nanoparticles larger than nm which are preferred for higher drug encapsulation efficiency and the ability to provide the sustained delivery of a wide array of drugs have been thought to be too large to rapidly diffuse through mucosal barriers.

Using self-assembled nucleic acid nanoparticles a single uniform population in size and shape having a precisely controlled spatial orientation and density of cancer-targeting ligands for enhanced delivery.

They may be single chain, multichain or branched and may form complexes, aggregates or any multi-unit structure once translated. In particular embodiments, T 1 is 0 oxoand T 2 is S thio or Se seleno.

USA1 – Modified polynucleotides encoding granulysin – Google Patents

Such a structure is termed the Cap1 structure. The plasmid contains Insertdesigned by the instant inventors. In another example, the modified nucleic acid and mmRNA may be suspended in a solution or medium with a cationic polymer, in a dry pharmaceutical composition or in a solution that is capable of being dried as described in U. Provided are methods for performing the titration, reduction or elimination of the immune response in a cell or a population of cells.

During RNA processing, a long chain of adenine nucleotides poly-A tail may be added to a polynucleotide such as an mRNA molecule in order to increase stability.