Modernatx, Inc.

Kanchana Ravichandran

Athanasios Dousis

Amy E Rabideau

Elissa Hobert

Michelle Lynn Hall

Margaret Franklin

Kevin Smith

Patrick Finn

Ding An

Paolo G V Martini

Raj Rajendran

The present disclosure provides, in some aspects, variant RNA polymerases, the use of which increases transcription efficiency while reducing the number of double-stranded RNA contaminates and run-on transcripts produced during an in vitro transcription reaction.

RNA polymerase variants

The present disclosure provides RNA polymerase variants for high efficiency transcription.

RNA polymerase variants for co-transcriptional capping

This disclosure relates to mRNA therapy for the treatment of hyperphenylalaninemias such as phenylketonuria (PKU). mRNAs for use in the invention, when administered in vivo, encode human phenylalanine hydroxylase (PAH), functional fragments thereof (e.g., those comprising the catalytic domain or the catalytic domain and the tetramerization domains), and fusion proteins comprising PAH. mRNAs of the invention are preferably encapsulated in lipid nanoparticles (LNPs) to effect efficient delivery to cells and/or tissues in subjects, when administered thereto. mRNA therapies of the invention increase and/or restore deficient levels of PAH expression and/or activity in subjects. mRNA therapies of the invention further decrease abnormal accumulation of phenylalanine associated with deficient PAH activity in subjects.

Polynucleotides encoding phenylalanine hydroxylase for the treatment of phenylketonuria

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Cambridge, MA, United States of America

Kanchana Ravichandran