Modernatx, Inc.

Moderna Therapeutics, Inc.

Stephane Bancel

Jason P Schrum

Tirtha Chakraborty

Atanu Roy

Antonin De Fougerolles

Kenechi Ejebe

Sayda Mahgoub Elbashir

Paul Hatala

Susan Whoriskey

Jeff Lynn Ellsworth

Justin Guild

Kristy M Wood

Matthias John

Noubar Boghos Afeyan

William Joseph Issa

Stephen G Hoge

John Grant Aunins

Alexander Aristarkhov

Ron Weiss

Yuxun Wang

Eric Yi-Chun Huang

Suhaib Siddiqi

Gregory Sieczkiewicz

The invention relates to compositions and methods for the manufacture and optimization of modified mRNA molecules via optimization of their terminal architecture.

Terminally modified RNA

Disclosed herein are methods for purifying RNA comprising poly A. Also disclosed herein are compositions such as surfaces and oligonucleotides for purifying RNA comprising polyA. Other embodiments are also disclosed. Commercially-available resins having polythymidine oligonucleotide ligands typically contain less than 30 thymidine (2′deoxy) residues and some commercial resin suppliers utilize a distribution of dT chain lengths, not of a discreet length.

Ribonucleic acid purification

Disclosed herein are methods for purifying RNA comprising poly A. Also disclosed herein are compositions such as surfaces and oligonucleotides for purifying RNA comprising polyA. Other embodiments are also disclosed. Commercially-available resins having polythymidine oligonucleotide ligands typically contain less than 30 thymidine (2'deoxy) residues and some commercial resin suppliers utilize a distribution of dT chain lengths, not of a discreet length.

Terminally Modified RNA

The present invention describes methods of removing DNA from an RNA transcript during the mRNA production process. The method embodies procedures for obtaining an in vitro transcription product, and removing any DNA from the product. The DNA can be removed by adding either free DNase or a resin containing immobilized DNase to the product, and recovering the RNA transcript. Alternatively, the DNA template used in the in vitro transcription reaction is labeled. After transcription, the product is applied to a resin that is configured to bind the label, and the RNA transcript is recovered. To detect whether any residual impurities are left in the RNA transcript product, the product is subjected to nuclease digestion and subsequently to liquid chromatography-tandem mass spectrometry analysis to quantitate any residual DNA. The present invention demonstrates efficient and effective methods of isolating an RNA transcript from an in vitro transcription product.

Removal of DNA fragments in mRNA production process

The invention relates to a pharmaceutical composition including a plurality of lipid nanoparticles having a mean particle size of between 80 nm and 160 nm and containing an mRNA encoding a polypeptide. The lipid nanoparticles include a cationic lipid, a neutral lipid, a cholesterol, and a PEG lipid. The mRNA contains a 5'-cap, 5&#x2032;-UTR, a 3&#x2032;-UTR, and a poly-A region with at least 100 nucleotides.

Modified Polynucleotides for the production of biologics and proteins associated with human disease

Provided are compositions and methods for delivering biological moieties such as modified nucleic acids into cells to kill or reduce the growth of microorganisms. Such compositions and methods include the use of modified messenger RNAs, and are useful to treat or prevent microbial infection, or to improve a subject's heath or wellbeing.

Engineered nucleic acids and methods of use thereof

Described are methods for production of RNA transcripts using a non-amplified, linearized DNA template in an in vitro transcription reaction. Enzymatic 5' capping and oligo dT purification can also be included in the methods.

Manufacturing methods for production of RNA transcripts

Provided are compositions and methods for delivering biological moieties such as modified nucleic acids into cells to modulate protein expression. Such compositions and methods include the use of modified messenger RNAs, and are useful to treat or prevent diseases, disorders or conditions, or to improve a subject's heath or wellbeing.

The invention relates to cosmetic mRNAs encoding elastin, and methods of using such mRNAs.

Modified polynucleotides for the production of cosmetic proteins and peptides

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

Growing community of inventors

Cambridge, MA, United States of America

Stephane Bancel