Document text
Principal Investigator: John Ramunas
Organization: REJUVENATION TECHNOLOGIES, INC.
Fiscal Year: 2024
Award: $324,998
Funding agency: National Institute of General Medical Sciences
Abstract
Rejuvenation Technologies Inc. (RTI) aims to expand the utility of our telomere extension biologic, telomerase
(TERT) mRNA, and our world-leading lipid nanoparticle (LNP) delivery vehicle by adding progenitor cell (PC)
targeting capability. Telomeres are the protective DNA tips of chromosomes essential for cell and lung health.
Telomeres shorten with each cell division, eventually exposing the DNA tip, which is detected as broken DNA,
with multiple deleterious consequences, many of which are known features of a number of diseases, such as
loss of progenitor cells, cellular senescence, secretion of molecules that activate fibroblasts, altered gene
expression, fibrosis, organ failure, and death. Critically short telomeres also drive further telomere shortening in
a vicious cycle. By targeting TERT mRNA to PCs, we can extend the regenerative capacity of these cells,
mitigating this vicious cycle and extending the healthspan. There is an unmet medical need for vehicles to deliver
therapeutic mRNA to PCs, the primary cells of regenerative medicine. PC-targeting vehicles could deliver mRNA
encoding any gene to PCs, fostering a new era of regenerative medicine. RTI has achieved a breakthrough in
mRNA delivery with the development of a novel, broadly-transfecting (BT)-LNP formulation. BT-LNPs have been
shown to transfect 16 tissues in non-human primates (NHPs), making them the only LNPs capable of transfecting
such a broad range of tissues to our knowledge. BT-LNPs are also well-tolerated in multiple species including
NHPs. RTI’s BT-LNP formulation can serve as a “base LNP” for targeting ligand attachment, conferring additional
cell type-specificity. By combining this with our TERT mRNA, which has shown highly successful rescue in
mouse models of both pulmonary and liver fibrosis, we seek to extend the regenerative capacity of various PC
types, addressing multiple disease indications. In this Phase I project, RTI will add PC targeting capability to our
BT-LNPs using the following approach: 1) Generate a library of rationally designed peptides targeting three PC
types. 2) Utilize a computational structural biology pipeline to screen candidate peptide targeting ligands in silico.
3) Add the candidate targeting ligands to our broadly-transfecting base vehicle BT-LNPs. 4) Perform an efficient,
sensitive in vivo screen to quantify the ability of each candidate LNP to transfect each of the 3 PC types. This
Phase I project will produce highly efficient, well-tolerated vehicles for in vivo delivery of mRNA to three PC
types, as well as a platform for efficient development of additional vehicles. This will both advance our novel
telomere extension biologic for multiple indications and allow us to pursue out-licensing for the CVs to potential
pharma and biotech partners.
Terms: <Address><Amino Acid Sequence><Antibodies><Assay><Bar Codes><Binding><Bioassay><Biological><Biological Assay><Biotech><Biotechnology><Blood><Blood Reticuloendothelial System><Body Tissues><Body Weight><Bone Marrow><Bone Marrow Reticuloendothelial System><Brain><Brain Nervous System><Cell Aging><Cell Body><Cell Growth in Number><Cell Isolation><Cell Multiplication><Cell Proliferation><Cell Segregation><Cell Senescence><Cell Separation><Cell Separation Technology><Cell Surface Proteins><Cell division><Cell surface><Cells><Cellular Aging><Cellular Proliferation><Cellular Senescence><Cessation of life><Chromosomes><Clinical><Computer Software Tools><DNA><Death><Deoxyribonucleic Acid><Development><Disease><Disorder><Dose><Encapsulated><Encephalon><Endosomes><Ensure><Fibroblasts><Fibrosis><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Formulation><Fostering><Gene Expression><Genes><Histopathology><IV Infusion><Immune Markers><Immunologic Markers><In Vitro><Intestinal><Intestines><Intravenous infusion procedures><Libraries><Licensing><Ligands><Lipids><Liver Fibrosis><Lung Tissue Fibrosis><Mediating><Medical><Messenger RNA><Methods><Mice><Mice Mammals><Microfluidics><Modeling><Molecular Configuration><Molecular Conformation><Molecular Interaction><Molecular Stereochemistry><Murine><Mus><Myeloid Progenitor><Myeloid Progenitor Cells><Myeloid Stem Cells><Neural Stem Cell><Organ failure><Peptides><Phase><Primary Protein Structure><Process><Progenitor Cells><Protein Binding Domain><Protein Binding Motif><Protein-Protein Interaction Domain><Proteins><Pulmonary Fibrosis><Receptosomes><Regenerative Medicine><Regenerative capacity><Rejuvenation><Replicative Senescence><Side><Software Tools><Solubility><Specificity><System><Technology><Telomerase><Telomere Shortening><Testing><Therapeutic><Time><Tissues><Toxicology><Transfection><Translations><barcode><base><bases><biologic><bowel><cell sorting><cell type><cellular targeting><clinical development><conformation><conformational><conformational state><conformationally><conformations><deliver mRNA><deliver messenger RNA><delivery system for mRNA><delivery vector><delivery vehicle><design><designing><developmental><drug discovery><fibrosis in the lung><fibrotic liver><flow cytophotometry><global health><health care economics><health-span><healthcare economics><healthspan><healthy life span><hepatic fibrosis><immune-based biomarkers><immunological biomarkers><immunological markers><in silico><in vitro testing><in vivo><intravenous infusion><lipid based nanoparticle><lipid nanoparticle><lung fibrosis><lung health><mRNA><mRNA delivery><magnetic beads><messenger RNA delivery><mouse model><murine model><myeloid stem and progenitor cell><nano particle delivery><nanoparticle delivered><nanoparticle delivery><nerve stem cell><neural precursor><neural precursor cell><neural progenitor><neural progenitor cells><neuron progenitors><neuronal progenitor><neuronal progenitor cells><neuronal stem cells><neuroprogenitor><non-human primate><nonhuman primate><novel><programs><protein sequence><pulmonary health><rational design><regeneration ability><regeneration capacity><regenerative cell><screening><screenings><software toolkit><stem><stem cells><structural biology><telomere><telomere attrition><translation><uptake><µfluidic>