Modified polynucleotides encoding cd28 molecule

Abstract

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation of U.S. patent application Ser. No. 13 / 791,910, filed Mar. 9, 2013, entitled Modified Polynucleotides for the Production of Proteins Associated with Human Disease which claims priority to U.S. Provisional Patent Application No. 61 / 681,742, filed, Aug. 10, 2012, entitled Modified Polynucleotides for the Production of Oncology-Related Proteins and Peptides, U.S. Provisional Patent Application No. 61 / 737,224, filed Dec. 14, 2012, entitled Terminally Optimized Modified RNAs, International Application No PCT / US2012 / 069610, filed Dec. 14, 2012, entitled Modified Nucleoside, Nucleotide, and Nucleic Acid Compositions, U.S. Provisional Patent Application No. 61 / 618,862, filed Apr. 2, 2012, entitled Modified Polynucleotides for the Production of Biologics, U.S. Provisional Patent Application No. 61 / 681,645, filed Aug. 10, 2012, entitled Modified Polynucleotides for the Production of Biologics, U.S. Provisional Pat...

AI Technical Summary

Benefits of technology

The patent describes methods and tools for designing, preparing, manufacturing, and formulating modified mRNA molecules. The technical effects of this invention include improved design of modified mRNA molecules for use in various applications, such as research and therapeutics, as well as improved methods for preparing and manufacturing such molecules. These improvements can lead to better outcomes and more efficient use of modified mRNA molecules in various settings.

Problems solved by technology

There are multiple problems with prior methodologies of effecting protein expression.

For example, introduced DNA can integrate into host cell genomic DNA at some frequency, resulting in alterations and / or damage to the host cell genomic DNA.

Not only do the multiple processing steps from administered DNA to protein create lag times before the generation of the functional protein, each step represents an opportunity for error and damage to the cell.

Further, it is known to be difficult to obtain DNA expression in cells as DNA frequently enters a cell but is not expressed or not expressed at reasonable rates or concentrations.

This can be a particular problem when DNA is introduced into primary cells or modified cell lines.

However, the low levels of translation and the immunogenicity of the molecules hampered the development of mRNA as a therapeutic and efforts have since focused on alternative applications that could instead exploit these pitfalls, i.e. immunization with mRNAs coding for cancer antigens.

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