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SNIM® RNA platform

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mRNA-based therapies are exciting alternatives to gene therapies and protein-based drugs with the potential to treat a wide array of diseases. Messenger RNA (mRNA) is a single strand of nucleotides, which copies genetic information from DNA and carries them to the cells’ protein-making machinery. Unique arrangements of mRNA nucleotide sequences can encode a variety of different proteins, which the body needs to function.

 

Historically, mRNA has not been usable as a therapeutic agent because when delivered into the body it is highly unstable and activates the immune system. In addition, to be functional, mRNA must enter the target cells of interest by crossing the cell membrane, which requires a carrier system to transport it into the cells. Following entry into the cell, the mRNA then needs to be released from this delivery system.

 

Ethris has developed two technology platforms to enable the use of mRNAs as a therapeutic agent: The Stabilized Non-Immunogenic mRNA (SNIM® RNA) platform as well as the complementary proprietary technologies for SNIM® RNA delivery. Our SNIM® RNA technology is a novel nucleic acid therapy platform based on stabilized non-immunogenic mRNA, which overcomes the innate instability and immunity of mRNA, due to chemical modifications in their structural elements. SNIM® RNAs can be administered repeatedly, leading to sustained production of therapeutically active proteins within the human body. Our technology can replace or augment missing or non-functional proteins that cause a disease, introduce new proteins to modulate the course of the disease or its symptoms and be used to develop vaccines.

STABILIZED NON-IMMUNOGENIC MESSENGER RNA – SNIM® RNA

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LNP platform

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Unleashing the full potential of an mRNA therapy is dependent on a delivery system that protects the cargo mRNA during transport to the target cells, facilitates entry through the cell’s membrane and efficiently releases it into the cell. Ethris has developed and optimized a delivery platform based on its proprietary lipidoid nanoparticle (LNP) platform technology with unique properties that allows efficient transport of mRNAs via inhalation to the respiratory tract as well as via intramuscular injection for vaccination.

Storage stability:

Storage and supply chain distribution of mRNA-based therapeutics is a known challenge. Ethris’ proprietary lipidoid formulation has a unique composition and stabilization mix that allows excellent mRNA stability at temperatures ranging from -20°C to room temperature. Ethris has additionally developed lyophilization and rapid rehydration processes providing product stability for long term storage and distribution at room temperature.

Application:

The effective delivery of nanoparticle-based drugs to the upper and lower respiratory tract displays an additional hurdle in their development profile, especially the generation of aerosols for inhalation while fully maintaining the integrity and quality of the lipidoid nanoparticle suspension. Ethris’ proprietary lipidoid formulation in combination with an optimized nebulization technology circumvents these hurdles and ensures delivery of potent, high quality and maximum integrity LNP aerosols into the respiratory tract.

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Manufacturing

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W. Zhang, R.E. De La Vega, M.J. Coenen, S.A. Muller, C.J. Peniche Silva, M.K. Aneja, C. Plank, M. van Griensven, C.H. Evans, E.R. Balmayor, An Improved, Chemically Modified RNA Encoding BMP-2 Enhances Osteogenesis In Vitro and In Vivo, Tissue Eng Part A, 25 (2019) 131-144. – Learn more.

Z. Trepotec, E. Lichtenegger, C. Plank, M.K. Aneja, C. Rudolph, Delivery of mRNA Therapeutics for the Treatment of Hepatic Diseases, Mol Ther, 27 (2019) 794-802. – Learn more.

Z. Trepotec, J. Geiger, C. Plank, M.K. Aneja, C. Rudolph, Segmented poly(A) tails significantly reduce recombination of plasmid DNA without affecting mRNA translation efficiency or half-life, RNA, 25 (2019) 507-518. – Learn more.

Z. Trepotec, M.K. Aneja, J. Geiger, G. Hasenpusch, C. Plank, C. Rudolph, Maximizing the Translational Yield of mRNA Therapeutics by Minimizing 5′-UTRs, Tissue Eng Part A, 25 (2019) 69-79. – Learn more.

E. Herbst, F.B. Imhoff, P. Foehr, S. Milz, C. Plank, C. Rudolph, G. Hasenpusch, J.P. Geiger, M.K. Aneja, K. Groth, S. Vogt, A.B. Imhoff, A. Schmitt, Chemically Modified Messenger RNA: Modified RNA Application for Treatment of Achilles Tendon Defects, Tissue Eng Part A, 25 (2019) 113-120. – Learn more.

M. Holstein, C. Mesa-Nunez, C. Miskey, E. Almarza, V. Poletti, M. Schmeer, E. Grueso, J.C. Ordonez Flores, D. Kobelt, W. Walther, M.K. Aneja, J. Geiger, H.B. Bonig, Z. Izsvak, M. Schleef, C. Rudolph, F. Mavilio, J.A. Bueren, G. Guenechea, Z. Ivics, Efficient Non-viral Gene Delivery into Human Hematopoietic Stem Cells by Minicircle Sleeping Beauty Transposon Vectors, Mol Ther, 26 (2018) 1137-1153. – Learn more.

K. Hirschberger, A. Jarzebinska, E. Kessel, V. Kretzschmann, M.K. Aneja, C. Dohmen, A. Herrmann-Janson, E. Wagner, C. Plank, C. Rudolph, Exploring Cytotoxic mRNAs as a Novel Class of Anti-cancer Biotherapeutics, Mol Ther Methods Clin Dev, 8 (2018) 141-151. – Learn more.

B. Connor, E. Firmin, A. McCaughey-Chapman, R. Monk, K. Lee, S. Liot, J. Geiger, C. Rudolph, K. Jones, Conversion of adult human fibroblasts into neural precursor cells using chemically modified mRNA, Heliyon, 4 (2018) e00918. – Learn more.

M. Utzinger, A. Jarzebinska, N. Haag, M. Schweizer, G. Winter, C. Dohmen, C. Rudolph, C. Plank, cmRNA/lipoplex encapsulation in PLGA microspheres enables transfection via calcium phosphate cement (CPC)/PLGA composites, J Control Release, 249 (2017) 143-149. – Learn more.

E. Schrom, M. Huber, M. Aneja, C. Dohmen, D. Emrich, J. Geiger, G. Hasenpusch, A. Herrmann-Janson, V. Kretzschmann, O. Mykhailyk, T. Pasewald, P. Oak, A. Hilgendorff, D. Wohlleber, H.G. Hoymann, D. Schaudien, C. Plank, C. Rudolph, R. Kubisch-Dohmen, Translation of Angiotensin-Converting Enzyme 2 upon Liver- and Lung-Targeted Delivery of Optimized Chemically Modified mRNA, Mol Ther Nucleic Acids, 7 (2017) 350-365. – Learn more.

K. Groth, T. Berezhanskyy, M.K. Aneja, J. Geiger, M. Schweizer, L. Maucksch, T. Pasewald, T. Brill, B. Tigani, E. Weber, C. Rudolph, G. Hasenpusch, Tendon healing induced by chemically modified mRNAs, Eur Cell Mater, 33 (2017) 294-307. – Learn more.

E.R. Balmayor, J.P. Geiger, C. Koch, M.K. Aneja, M. van Griensven, C. Rudolph, C. Plank, Modified mRNA for BMP-2 in Combination with Biomaterials Serves as a Transcript-Activated Matrix for Effectively Inducing Osteogenic Pathways in Stem Cells, Stem Cells Dev, 26 (2017) 25-34. – Learn more.

Z.S. Badieyan, T. Pasewald, O. Mykhaylyk, C. Rudolph, C. Plank, Efficient ex vivo delivery of chemically modified messenger RNA using lipofection and magnetofection, Biochem Biophys Res Commun, 482 (2017) 796-801. – Learn more.

A. Jarzebinska, T. Pasewald, J. Lambrecht, O. Mykhaylyk, L. Kummerling, P. Beck, G. Hasenpusch, C. Rudolph, C. Plank, C. Dohmen, A Single Methylene Group in Oligoalkylamine-Based Cationic Polymers and Lipids Promotes Enhanced mRNA Delivery, Angew Chem Int Ed Engl, 55 (2016) 9591-9595. – Learn more.

M. Ferizi, M.K. Aneja, E.R. Balmayor, Z.S. Badieyan, O. Mykhaylyk, C. Rudolph, C. Plank, Human cellular CYBA UTR sequences increase mRNA translation without affecting the half-life of recombinant RNA transcripts, Sci Rep, 6 (2016) 39149. – Learn more.

E.R. Balmayor, J.P. Geiger, M.K. Aneja, T. Berezhanskyy, M. Utzinger, O. Mykhaylyk, C. Rudolph, C. Plank, Chemically modified RNA induces osteogenesis of stem cells and human tissue explants as well as accelerates bone healing in rats, Biomaterials, 87 (2016) 131-146. – Learn more.

Z.S. Badieyan, T. Berezhanskyy, M. Utzinger, M.K. Aneja, D. Emrich, R. Erben, C. Schuler, P. Altpeter, M. Ferizi, G. Hasenpusch, C. Rudolph, C. Plank, Transcript-activated collagen matrix as sustained mRNA delivery system for bone regeneration, J Control Release, 239 (2016) 137-148. – Learn more.

M. Ferizi, C. Leonhardt, C. Meggle, M.K. Aneja, C. Rudolph, C. Plank, J.O. Radler, Stability analysis of chemically modified mRNA using micropattern-based single-cell arrays, Lab Chip, 15 (2015) 3561-3571. – Learn more.

The success of mRNA therapeutics is highly dependent on stable supply chains and manufacturing capabilities. Ethris has established a supply chain for its raw materials as well as excipients and developed fully-owned, stable and scalable, HPLC-free upstream and downstream manufacturing processes that enable the production of high-quality product candidates for clinical supply. Ethris also works closely with a network of qualified contract development and manufacturing organizations (CDMOs) to ensure the highest quality control for its product candidates.

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Scientific publications

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W. Zhang, R.E. De La Vega, M.J. Coenen, S.A. Muller, C.J. Peniche Silva, M.K. Aneja, C. Plank, M. van Griensven, C.H. Evans, E.R. Balmayor, An Improved, Chemically Modified RNA Encoding BMP-2 Enhances Osteogenesis In Vitro and In Vivo, Tissue Eng Part A, 25 (2019) 131-144. – Learn more.

Z. Trepotec, E. Lichtenegger, C. Plank, M.K. Aneja, C. Rudolph, Delivery of mRNA Therapeutics for the Treatment of Hepatic Diseases, Mol Ther, 27 (2019) 794-802. – Learn more.

Z. Trepotec, J. Geiger, C. Plank, M.K. Aneja, C. Rudolph, Segmented poly(A) tails significantly reduce recombination of plasmid DNA without affecting mRNA translation efficiency or half-life, RNA, 25 (2019) 507-518. – Learn more.

Z. Trepotec, M.K. Aneja, J. Geiger, G. Hasenpusch, C. Plank, C. Rudolph, Maximizing the Translational Yield of mRNA Therapeutics by Minimizing 5′-UTRs, Tissue Eng Part A, 25 (2019) 69-79. – Learn more.

E. Herbst, F.B. Imhoff, P. Foehr, S. Milz, C. Plank, C. Rudolph, G. Hasenpusch, J.P. Geiger, M.K. Aneja, K. Groth, S. Vogt, A.B. Imhoff, A. Schmitt, Chemically Modified Messenger RNA: Modified RNA Application for Treatment of Achilles Tendon Defects, Tissue Eng Part A, 25 (2019) 113-120. – Learn more.

M. Holstein, C. Mesa-Nunez, C. Miskey, E. Almarza, V. Poletti, M. Schmeer, E. Grueso, J.C. Ordonez Flores, D. Kobelt, W. Walther, M.K. Aneja, J. Geiger, H.B. Bonig, Z. Izsvak, M. Schleef, C. Rudolph, F. Mavilio, J.A. Bueren, G. Guenechea, Z. Ivics, Efficient Non-viral Gene Delivery into Human Hematopoietic Stem Cells by Minicircle Sleeping Beauty Transposon Vectors, Mol Ther, 26 (2018) 1137-1153. – Learn more.

K. Hirschberger, A. Jarzebinska, E. Kessel, V. Kretzschmann, M.K. Aneja, C. Dohmen, A. Herrmann-Janson, E. Wagner, C. Plank, C. Rudolph, Exploring Cytotoxic mRNAs as a Novel Class of Anti-cancer Biotherapeutics, Mol Ther Methods Clin Dev, 8 (2018) 141-151. – Learn more.

B. Connor, E. Firmin, A. McCaughey-Chapman, R. Monk, K. Lee, S. Liot, J. Geiger, C. Rudolph, K. Jones, Conversion of adult human fibroblasts into neural precursor cells using chemically modified mRNA, Heliyon, 4 (2018) e00918. – Learn more.

M. Utzinger, A. Jarzebinska, N. Haag, M. Schweizer, G. Winter, C. Dohmen, C. Rudolph, C. Plank, cmRNA/lipoplex encapsulation in PLGA microspheres enables transfection via calcium phosphate cement (CPC)/PLGA composites, J Control Release, 249 (2017) 143-149. – Learn more.

E. Schrom, M. Huber, M. Aneja, C. Dohmen, D. Emrich, J. Geiger, G. Hasenpusch, A. Herrmann-Janson, V. Kretzschmann, O. Mykhailyk, T. Pasewald, P. Oak, A. Hilgendorff, D. Wohlleber, H.G. Hoymann, D. Schaudien, C. Plank, C. Rudolph, R. Kubisch-Dohmen, Translation of Angiotensin-Converting Enzyme 2 upon Liver- and Lung-Targeted Delivery of Optimized Chemically Modified mRNA, Mol Ther Nucleic Acids, 7 (2017) 350-365. – Learn more.

K. Groth, T. Berezhanskyy, M.K. Aneja, J. Geiger, M. Schweizer, L. Maucksch, T. Pasewald, T. Brill, B. Tigani, E. Weber, C. Rudolph, G. Hasenpusch, Tendon healing induced by chemically modified mRNAs, Eur Cell Mater, 33 (2017) 294-307. – Learn more.

E.R. Balmayor, J.P. Geiger, C. Koch, M.K. Aneja, M. van Griensven, C. Rudolph, C. Plank, Modified mRNA for BMP-2 in Combination with Biomaterials Serves as a Transcript-Activated Matrix for Effectively Inducing Osteogenic Pathways in Stem Cells, Stem Cells Dev, 26 (2017) 25-34. – Learn more.

Z.S. Badieyan, T. Pasewald, O. Mykhaylyk, C. Rudolph, C. Plank, Efficient ex vivo delivery of chemically modified messenger RNA using lipofection and magnetofection, Biochem Biophys Res Commun, 482 (2017) 796-801. – Learn more.

A. Jarzebinska, T. Pasewald, J. Lambrecht, O. Mykhaylyk, L. Kummerling, P. Beck, G. Hasenpusch, C. Rudolph, C. Plank, C. Dohmen, A Single Methylene Group in Oligoalkylamine-Based Cationic Polymers and Lipids Promotes Enhanced mRNA Delivery, Angew Chem Int Ed Engl, 55 (2016) 9591-9595. – Learn more.

M. Ferizi, M.K. Aneja, E.R. Balmayor, Z.S. Badieyan, O. Mykhaylyk, C. Rudolph, C. Plank, Human cellular CYBA UTR sequences increase mRNA translation without affecting the half-life of recombinant RNA transcripts, Sci Rep, 6 (2016) 39149. – Learn more.

E.R. Balmayor, J.P. Geiger, M.K. Aneja, T. Berezhanskyy, M. Utzinger, O. Mykhaylyk, C. Rudolph, C. Plank, Chemically modified RNA induces osteogenesis of stem cells and human tissue explants as well as accelerates bone healing in rats, Biomaterials, 87 (2016) 131-146. – Learn more.

Z.S. Badieyan, T. Berezhanskyy, M. Utzinger, M.K. Aneja, D. Emrich, R. Erben, C. Schuler, P. Altpeter, M. Ferizi, G. Hasenpusch, C. Rudolph, C. Plank, Transcript-activated collagen matrix as sustained mRNA delivery system for bone regeneration, J Control Release, 239 (2016) 137-148. – Learn more.

M. Ferizi, C. Leonhardt, C. Meggle, M.K. Aneja, C. Rudolph, C. Plank, J.O. Radler, Stability analysis of chemically modified mRNA using micropattern-based single-cell arrays, Lab Chip, 15 (2015) 3561-3571. – Learn more.

mRNA design

  1. Z. Trepotec, J. Geiger, C. Plank, M.K. Aneja, C. Rudolph, Segmented poly(A) tails significantly reduce recombination of plasmid DNA without affecting mRNA translation efficiency or half-life, RNA, 25 (2019) 507-518. – Learn more.
  2. Z. Trepotec, M.K. Aneja, J. Geiger, G. Hasenpusch, C. Plank, C. Rudolph, Maximizing the Translational Yield of mRNA Therapeutics by Minimizing 5′-UTRs, Tissue Eng Part A, 25 (2019) 69-79. – Learn more.
  3. E. Schrom, M. Huber, M. Aneja, C. Dohmen, D. Emrich, J. Geiger, G. Hasenpusch, A. Herrmann-Janson, V. Kretzschmann, O. Mykhailyk, T. Pasewald, P. Oak, A. Hilgendorff, D. Wohlleber, H.G. Hoymann, D. Schaudien, C. Plank, C. Rudolph, R. Kubisch-Dohmen, Translation of Angiotensin-Converting Enzyme 2 upon Liver- and Lung-Targeted Delivery of Optimized Chemically Modified mRNA, Mol Ther Nucleic Acids, 7 (2017) 350-365. – Learn more.
  4. M. Ferizi, M.K. Aneja, E.R. Balmayor, Z.S. Badieyan, O. Mykhaylyk, C. Rudolph, C. Plank, Human cellular CYBA UTR sequences increase mRNA translation without affecting the half-life of recombinant RNA transcripts, Sci Rep, 6 (2016) 39149. – Learn more.
  5. M. Ferizi, C. Leonhardt, C. Meggle, M.K. Aneja, C. Rudolph, C. Plank, J.O. Radler, Stability analysis of chemically modified mRNA using micropattern-based single-cell arrays, Lab Chip, 15 (2015) 3561-3571. – Learn more.

mRNA delivery

  1. Z. Trepotec, E. Lichtenegger, C. Plank, M.K. Aneja, C. Rudolph, Delivery of mRNA Therapeutics for the Treatment of Hepatic Diseases, Mol Ther, 27 (2019) 794-802. – Learn more.
  2. M. Holstein, C. Mesa-Nunez, C. Miskey, E. Almarza, V. Poletti, M. Schmeer, E. Grueso, J.C. Ordonez Flores, D. Kobelt, W. Walther, M.K. Aneja, J. Geiger, H.B. Bonig, Z. Izsvak, M. Schleef, C. Rudolph, F. Mavilio, J.A. Bueren, G. Guenechea, Z. Ivics, Efficient Non-viral Gene Delivery into Human Hematopoietic Stem Cells by Minicircle Sleeping Beauty Transposon Vectors, Mol Ther, 26 (2018) 1137-1153. – Learn more.
  3. M. Utzinger, A. Jarzebinska, N. Haag, M. Schweizer, G. Winter, C. Dohmen, C. Rudolph, C. Plank, cmRNA/lipoplex encapsulation in PLGA microspheres enables transfection via calcium phosphate cement (CPC)/PLGA composites, J Control Release, 249 (2017) 143-149. – Learn more.
  4. Z.S. Badieyan, T. Pasewald, O. Mykhaylyk, C. Rudolph, C. Plank, Efficient ex vivo delivery of chemically modified messenger RNA using lipofection and magnetofection, Biochem Biophys Res Commun, 482 (2017) 796-801. – Learn more.
  5. A. Jarzebinska, T. Pasewald, J. Lambrecht, O. Mykhaylyk, L. Kummerling, P. Beck, G. Hasenpusch, C. Rudolph, C. Plank, C. Dohmen, A Single Methylene Group in Oligoalkylamine-Based Cationic Polymers and Lipids Promotes Enhanced mRNA Delivery, Angew Chem Int Ed Engl, 55 (2016) 9591-9595. – Learn more.

Learn more about our pipeline.

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