Modernatx, Inc.

Shire Human Genetic Therapies, Inc.

Synageva Biopharma Corporation

Fundacion Para La Investigacion Medica Aplicada

Paolo Martini

Vladimir Presnyak

Kerry Benenato

Stephen G Hoge

Ellalahewage Sathyajith Kumarasinghe

Iain McFadyen

Staci Sabnis

Michael F Concino

Lin Tung Guey

Pericles Calias

Muthuraman Meiyappan

Bettina Strack-Logue

Ding An

Alla Romashko

Xuling Zhu

Jing Pan

Angela Norton

Richard Pfeifer

Bohong Zhang

Kevin Holmes

Andrea Iskenderian

Dianna Lundberg

Huang Yan

Mary Alessandrini

Jingsong Cao

Michael W Heartlein

Lawrence Charnas

Pedro Berraondo Lopez

Marcia Sellos-Moura

Jan Powell

Juan Ruiz

Antonio Fontanellas Roma

Brian Felice

Pan Luying

Scott Alderucci

Brian Pescatore

Nancy Savioli

Luying Pan

Lei Jiang

Matias Antonio Avila Zaragoza

Iain Mcfadyen

Yan Huang

The invention relates to mRNA therapy for the treatment of Acute Intermittent Porphyria (AIP). mRNAs for use in the invention, when administered in vivo, encode human porphobilinogen deaminase (PBGD), isoforms thereof, functional fragments thereof, and fusion proteins comprising PBGD. mRNAs of the invention are preferably encapsulated in lipid nanoparticles (LNPs) to affect efficient delivery to cells and/or tissues in subjects, when administered thereto. mRNA therapies of the invention increase and/or restore deficient levels of PBGD expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of toxic metabolites associated with deficient PBGD activity in subjects, namely porphobilinogen and aminolevulinate (PBG and ALA).

Polynucleotides encoding porphobilinogen deaminase for the treatment of acute intermittent porphyria

The invention relates to mRNA therapy for the treatment of galactosemia type 1 (Gal-1). mRNAs for use in the invention, when administered in vivo, encode human galactose-1-phosphate uridylyltransferase (GALT), isoforms thereof, functional fragments thereof, and fusion proteins comprising GALT. 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 GALT expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of toxic metabolites associated with deficient GALT activity in subjects, namely galactose-1-phosphate (Gal-1-P).

Polynucleotides encoding galactose-1-phosphate uridylyltransferase for the treatment of galactosemia type 1

The invention relates to mRNA therapy for the treatment of Citrullinemia Type 2 ('CTLN2'). mRNAs for use in the invention, when administered in vivo, encode human Citrin, isoforms thereof, functional fragments thereof, and fusion proteins comprising Citrin. 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 Citrin expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of biomarkers associated with deficient Citrin activity in subjects, namely ammonia and/or triglycerides.

Polynucleotides encoding Citrin for the treatment of Citrullinemia type 2

The invention relates to mRNA therapy for the treatment of Alagille syndrome (ALGS), mRNAs for use in the invention, when administered in vivo, encode JAGGED 1 (JAG1), isoforms thereof functional fragments thereof, and fusion proteins comprising JAG1, 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 JAG1 expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of toxic metabolites associated with deficient JAG1 activity in subjects.

Polynucleotides encoding JAGGED1 for the treatment of Alagille syndrome

The invention relates to mRNA therapy for the treatment of hyperlipidemia. mRNAs for use in the invention, when administered in vivo, encode human lipoprotein lipase (LPL), isoforms thereof, functional fragments thereof, and fusion proteins comprising LPL. 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 LPL expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of triglycerides associated with deficient LPL activity in subjects.

Polynucleotides encoding lipoprotein lipase for the treatment of hyperlipidemia

The invention relates to mRNA therapy for the treatment of cystic fibrosis. mRNAs for use in the invention, when administered in vivo, encode cystic fibrosis transmembrane conductance regulator (CFTR), isoforms thereof, functional fragments thereof, and fusion proteins comprising CFTR. 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 CFTR expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of toxic metabolites associated with deficient CFTR activity in subjects.

Polynucleotides encoding cystic fibrosis transmembrane conductance regulator for the treatment of cystic fibrosis

The invention relates to mRNA therapy for the treatment of Fabry disease. mRNAs for use in the invention, when administered in vivo, encode human the &#x3b1;-galactosidase A (GLA), isoforms thereof, functional fragments thereof, and fusion proteins comprising GLA. 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 GLA expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of toxic metabolites associated with deficient GLA activity in subjects, namely Gb3 and lyso-Gb3.

Polynucleotides encoding &#x3b1;-galactosidase A for the treatment of Fabry disease

The disclosure relates to polynucleotides comprising an open reading frame of linked nucleosides encoding human methylmalonyl-CoA mutase precursor, human methylmalonyl-CoA mutase (MCM) mature form, or functional fragments thereof. In some embodiments, the disclosure includes methods of treating methylmalonic acidemia in a subject in need thereof comprising administering an mRNA encoding an MCM polypeptide.

Polynucleotides encoding methylmalonyl-CoA mutase

Among other things, the present invention provides methods and compositions of treating Sanfilippo syndrome type B (Sanfilippo B) by, e.g., intrathecal (IT) administration of a Naglu protein. A suitable Naglu protein can be a recombinant, gene-activated or natural protein. In some embodiments, a suitable Naglu protein is a recombinant Naglu protein. In some embodiments, a recombinant Naglu protein is a fusion protein containing a Naglu domain and a lysosomal targeting moiety. In some embodiments, the lysosomal targeting domain is an IGF-II moiety.

Therapeutic fusion protein comprising an alpha-n-acetylglucosaminidase and a lysosomal targeting moiety

Polynucleotides encoding citrin for the treatment of Citrullinemia type 2

Polynucleotides encoding alpha-galactosidase A for the treatment of Fabry disease

Growing community of inventors

Boston, MA, United States of America

Paolo Martini