Intellectual Property
“Serum Response Factor Regenerates Senescent Cells," U.S. Application
No.:/U.S. Patent No.: 62/614,190, filed/Issued: Filed, Inventors: Robert Schwartz, Dinaker Iyer, UHID: 2018-010.
“Bioreactor for Stem Cell Expansion” Owned by Synthecon, Inc. and licensed to Animatus Biosciences. U.S. Patent No.: 10,214,715.
“Enhanced Cardiomyocyte Regeneration” US Patent No.: 2021/0187123A1
Publications
Brief report: SRF-dependent MiR-210 silences the sonic hedgehog signaling during cardiopoesis. Zheng G, Tao Y, Yu W, Schwartz RJ. Stem Cells. 2013; 31:2279-85.
Protein tyrosine phosphatase-like A regulates myoblast proliferation and differentiation through MyoG and the cell cycling signaling pathway. Lin X, Yang X, Li Q, Ma Y, Cui S, He D, Lin X, Schwartz RJ, Chang J. Mol Cell Biol. 2012; 32:297-308.
Serum response factor orchestrates nascent sarcomerogenesis and silences the biomineralization gene program in the heart. Niu Z1, Iyer D, Conway SJ, Martin JF, Ivey K, Srivastava D, Nordheim A, Schwartz RJ. Proc Natl Acad Sci U S A. 2008;105:17824-9.
SMYD1, the myogenic activator, is a direct target of serum response factor and myogenin.
Li D, Niu Z, Yu W, Qian Y, Wang Q, Li Q, Yi Z, Luo J, Wu X, Wang Y, Schwartz RJ, Liu M. Nucleic Acids Res. 2009; 37:7059-71.
Identification of direct serum response factor gene targets during DMSO induced P19 cardiac cell differentiation. Zhang, S.X., Gras, E,G., Wycuff, D.R., Marriot, S.J., Kadeer, N., Yu, W., Olson, E.N., Garry, D.J., Parmacek, M.S. and Schwartz, RJ. 2005; J. Biol. Chem. 280, 19115 – 19126.
PKG-1α mediates the transcriptional activity of GATA4. Yanlin, Ma, Y Wang, J, Yanhong, Y, Schwartz, RJ. 2016; Cellular Signaling 8:585-594.
Conversion of human cardiac progenitor cells into cardiac pacemaker-like cells. Raghunathan S, Islas JF, Mistretta B, Iyer D, ShiL, Gunaratne PH, Ko G, Schwartz RJ, McConnel BK. J Mol Cell Cardiol 2019; 138: -12-32
Beta-Adrenergic stimuli and rotating suspension culture enhance conversion of human adipogenic mesenchymal stem cells into highly conductive cardiac progenitors. Islas JF, Abbasgjolizadeh R, Dasco C, Potaman VN, Navran S, Bond RA, Iyer D, Birla R, Schwartz. J Tissue Eng Regen Med. 2020; 14:306-318.
A Highly Conductive 3D Cardiac Patch Fabricated Using Cardiac Myocytes Reprogrammed from Human Adipogenic Mesenchymal Stem Cells. Abbasgolizadh R, Islas JF, Navran S, Potaman VN, Schwartz RJ, Birla RK. Cardiovas Eng Technol 2020; 11: 205-218.
Mutant SRF and YAP synthetic modified mRNAs drive nuclear replication. Xiao S, Liang R, Muili AB, Cao X, Navran, S, Schwartz RJ, Iyer D. J Cardiovasc Aging 2022;2:29
STEMIN and YAP 5SA synthetic modified mRNAs regenerate and repair infarcted mouse hearts. Xiao S, Liang R, Lucero E, McConnell BK, Chen Z, Chang J, Navran S, Schwartz RJ, Iyer D. J Cardiovasc Aging 2022;2:31.
Future Research Directions
Heart Related
Heart Failure in aging without mycardial infarction.
Hypoplastic Left Heart Syndrome - congenital underdevelopment of the left ventricle in newborns. Can be addressed with regenerative mmRNAs.
Cardiac arrythmias - Animatus has technology to reprogram adipose (fat) stem cells using mmRNAs to electrically conductive heart cells that can replace faulty cells that cause arrythmias.
Non Heart Related
The same gene networks that reprogram heart cells also exist in other tissues in the body, such as blood vessels, skeletal muscle,liver, nerves, pancreas, intestine, skin, immune cells and lung. Therefore, these same mmRNAs that work in the heart could potentially be used to regenerate these tissues as well.
Modifications to mRNAs discovered by Animatus could target any therapeutic mRNA to a specific tissue. This would mean that an mRNA could be administered systemically and produce an effect only in the targeted tissue.
Many years of research by Animatus' scientists have given us a deep understanding of cardiac developmental biology. We have applied this expertise to develop technology that can control networks of genes to regenerate cardiac tissue.
A messenger RNA directs a cell to make a specific protein. Our two mRNA combination, AN-153, are modified to make altered proteins which regulate key cellular pathways in cardiac cells.
These mutant proteins, when expressed in a cardiac cell, cause activation of gene networks that drive production of many stem cell proteins that rejuvenates injured heart tissue.
Unlike normal adult cardiac cells, the reprogrammed cardiac stem cells can replicate and replace cells injured by a heart attack. Once the AN-153 mRNAs have decayed, the stem cells will revert to a normal cardiac cell type and restore the function of the heart.
Mice with a myocardial infarct were followed for 4 weeks. The mice treated with the synthetic mRNA combination, AN-153 showed complete recovery of cardiac output (Ejection Fraction) and restoration of normal cardiac architecture.
How will the mRNA be administered to a patient?
The mRNA will be injected directly in the heart via a catheterization procedure that is similar to those performed in hospitals thousands of times a year.
