Biontech Se

Biontech Rna Pharmaceuticals Gmbh

Biontech Ag

Tron—translationale Onkologie an Der Universitátsmedizin Der Johannes Gutenberg—universität Mainz Gemeinnützige Gmbh

Tron-translationale Onkologie an Der Universitatsmedizin Der Johannes Gutenberg-universitat Mainz

Tron Translationale Onkologie an Der Universitatsm

Ganymed Pharmaceuticals Ag

Universitätsmedizin Der Johannes Gutenberg-universitat Mainz

Tron—translationale Onkologie an Der Universitatsmedizin Der Johannes Gutenberg-universitat Mainz Ggmbh

Ganymed Pharmaceuticals Gmbh

Translationale Onkologie an Der Universitätsmedizin Der Johannes Gutenberg-universität Mainz Gemeinnützige Gmbh

Tron Ggmbh

Moniech Rna Pharmecenticais Gmbh

Tron—translationale Onkologic an Der Universitätsmedzin Der Johannes Gutenberg-universität Mainz Gemcinnützige Gmbh

Astellas Pharma Gmbh

Tim Beissert

Ugur Sahin

Marco Alexander Poleganov

Ozlem Tureci

Özlem Türeci

Mario Perkovic

Markus Fiedler

Fabrice Le Gall

Christiane Regina Stadler

Arne Jendretzki

Laura Plum

Hayat Bähr-Mahmud

Julia Holland

Lars Koste

Stephanie Herz

Marco Poleganov

Andreas Kuhn

Britta Vallazza

Ozlem Türeci

Stephanie Fesser

Alexandra Orlandini Von Niessen

Hayat Bahr-Mahmud

Methods for effecting the de-differentiation of somatic cells to cells having stem cell characteristics, in particular pluripotency, include the steps of introducing RNA encoding factors inducing the de-differentiation of somatic cells into the somatic cells and culturing the somatic cells allowing the cells to de-differentiate.

Use of RNA for reprogramming somatic cells

The present invention relates to systems and methods suitable for high-level protein production. In particular, a system comprising two separate RNA molecules is foreseen, each comprising a nucleotide sequence derived from an alphavirus: one RNA molecule comprises a RNA construct for expressing alphavirus replicase, and one RNA molecule comprises a RNA replicon that can be replicated by the replicase in trans. The system of the present invention enables expression of a protein of interest in a cell or organism, but is not associated with undesired virus-particle formation. The present invention is suitable for efficiently and safely producing a protein of interest in a target organism. Respective methods of protein production in vitro and in vivo as well as medical uses are provided herein. The present invention also provides DNA encoding the RNA molecules of the invention, and cells comprising the RNA molecules of the invention.

Trans-replicating RNA

The present invention embraces a RNA replicon that can be replicated by a replicase of alphavirus origin and comprises an open reading frame encoding a reprogramming factor. Such RNA replicons are useful for expressing a reprogramming factor in a cell, in particular a somatic cell. Cells engineered to express such reprogramming factors are useful in cell transplantation therapies.

RNA replicon for reprogramming somatic cells

The present invention embraces a RNA replicon that can be replicated by a replicase of alphavirus origin. The RNA replicon comprises sequence elements required for replication by the replicase, but these sequence elements do not encode any protein or fragment thereof, such as an alphavirus non-structural protein or fragment thereof. Thus, in the RNA replicon according to the invention, sequence elements required for replication by the replicase and protein-coding region(s) are uncoupled. According to the present invention the uncoupling is achieved by the removal of at least one initiation codon compared to a native alphavirus genomic RNA. In particular, the RNA replicon comprises a 5' replication recognition sequence, wherein the 5′ replication recognition sequence is characterized in that it comprises the removal of at least one initiation codon compared to a native alphavirus 5′ replication recognition sequence. The replicase of alphavirus origin may be encoded by an open reading frame on the RNA replicon or on a separate RNA molecule. The present invention enables efficient and safe expression of a protein of interest in a cell or organism, but is not associated with undesired production of fragments of alphavirus non-structural protein. Methods of protein production in vitro and in vivo, as well as medical uses, are provided herein.

RNA replicon for versatile and efficient gene expression

The present invention relates to stabilization of RNA, in particular mRNA, and an increase in mRNA translation. The present invention particularly relates to a modification of RNA, in particular in vitro-transcribed RNA, resulting in increased transcript stability and/or translation efficiency. According to the invention, it was demonstrated that certain sequences in the 3'-untranslated region (UTR) of an RNA molecule improve stability and translation efficiency.

3'-UTR sequences for stabilization of RNA

The present invention embraces a RNA replicon that can be replicated by a replicase of alphavirus origin. The RNA replicon comprises sequence elements required for replication by the replicase, but these sequence elements do not encode any protein or fragment thereof, such as an alphavirus non-structural protein or fragment thereof. Thus, in the RNA replicon according to the invention, sequence elements required for replication by the replicase and protein-coding region(s) are uncoupled. According to the present invention the uncoupling is achieved by the removal of at least one initiation codon compared to a native alphavirus genomic RNA. In particular, the RNA replicon comprises a 5' replication recognition sequence, wherein the 5&#x2032; replication recognition sequence is characterized in that it comprises the removal of at least one initiation codon compared to a native alphavirus 5&#x2032; replication recognition sequence. The replicase of alphavirus origin may be encoded by an open reading frame on the RNA replicon or on a separate RNA molecule. The present invention enables efficient and safe expression of a protein of interest in a cell or organism, but is not associated with undesired production of fragments of alphavirus non-structural protein. Methods of protein production in vitro and in vivo, as well as medical uses, are provided herein.

The present invention provides methods for de-differentiating somatic cells into stem-like cells without generating embryos or fetuses. More specifically, the present invention provides methods for effecting the de-differentiation of somatic cells to cells having stem cell characteristics, in particular pluripotency, by introducing RNA encoding factors inducing the de-differentiation of somatic cells into the somatic cells and culturing the somatic cells allowing the cells to de-differentiate.

The present invention relates to expressing RNA in cells and, in particular, enhancing viability of cells in which RNA is to be expressed. Specifically, the present invention provides methods for expressing RNA in cells comprising the steps of preventing engagement of IFN receptor by extracellular IFN and inhibiting intracellular IFN signalling in the cells. Thus, preventing engagement of IFN receptor by extracellular IFN and inhibiting intracellular IFN signalling in the cells allows repetitive transfer of RNA into the cells.

Method for cellular RNA expression

The present invention provides binding agents that contain n binding domain that is specific for CD3 allowing binding to T cells and a binding domain that is specific for a tumor-associated claudin molecule and methods of using these binding agents or nucleic acids encoding therefor for treating cancer.

Agents for treatment of claudin expressing cancer diseases

The present invention provides binding agents that contain a binding domain that is specific for CD3 allowing binding to T cells and a binding domain that is specific for a tumor-associated claudin molecule and methods of using these binding agents or nucleic acids encoding therefor for treating cancer.

Growing community of inventors

Gross-Gerau, Germany

Tim Beissert