Matthew Levy

Matthew Levy, Ph.D.

Location

  • Vitrisa Therapeutics Durham, NC 27701

Research Profiles

Research Profiles

Research Profiles

 PubMed

PubMed.gov Portal

Professional Interests

The Levy Lab is focused on developing new technologies and approaches using nucleic acid aptamers as well as engineered proteins for both diagnostic and therapeutic purposes. I have been working with, synthesizing and engineering aptamers, ribozymes and deoxyribozymes and engineering proteins for more than 16 years. Prior to this, I spent a number of years investigating the prebiotic synthesis and stability of the nucleobases in RNA and DNA. My current lab is focused on developing new methods as well as new aptamers which target cells, engineering aptamer based biosensors and engineering proteins. I was among the first to demonstrate the targeted delivery of cargoes to cells using receptor-specific aptamers during my postdoctoral work, coupling nuclease stabilized aptamers that target the prostate specific membrane antigen (PSMA) to quantum dots for imaging or to the ribosomal toxin gelonin for use as a therapeutic. I continue to seek better and more robust ways to find affinity agents that can specifically target cells. We have developed novels methods to identify RNA molecules which are directly internalized by cells (1) and have also selected aptamers to some therapeutically relevant protein targets including the human transferrin receptor (CD71) (2, 3), a protein over expressed on many cancers and the target receptor for mammarenavirus entry, the dendritic cell receptor DEC205 a potentially important target for the generation of vaccines (4). The lab is now adapting many of these molecules for both diagnostic and therapeutic applications including generating novel imaging agents, aptamer targeted toxins (5), liposomes (2) and engineering oligonucleotide stabilized lipid micelles (6)  for the delivery of drugs, siRNA and mRNA. Our focus, however, is not just limited to using aptamers as targeting agents.  For example, we recently published a study demonstrating the ability to target siRNA-laden LNPs to DEC205+ DC in mice using an anti-DEC205 single chain antibody (7).  Most recently, we have developed an improved means to identify highly stabilized, modified aptamers with enhanced chemical functionality.  Importantly, the approach allows us to rapidly generate highly stable ligands to targets that we could not previously hit.  This is a very active area in my group in which we are working with other acedemics as well as partnering with industry. Finally, in addition to using aptamers as ‘tools’, my lab has a standing interest in better understanding the unique nature of aptamer-protein interactions. In this respect, we have a number of active projects in which we are using structural approaches (crystallography and NMR) to better understand the unique nature of these non-natural nucleic acid:protein interactions (8).

  1.   Magalhães ML, Byrom M, Yan A, Kelly L, Li N, Furtado R, Palliser D, Ellington AD, Levy M. A general RNA motif for cellular transfection. Mol Ther. 2012 Mar;20(3):616-24. PubMed PMID: 22233578; PubMed Central PMCID: PMC3294222.
  2. Wilner SE, Wengerter B, Maier K, de Lourdes Borba Magalhães M, Del Amo DS, Pai S, Opazo F, Rizzoli SO, Yan A, Levy M. An RNA alternative to human transferrin: a new tool for targeting human cells. Mol Ther Nucleic Acids. 2012 May 15;1:e21. PubMed PMID: 23344001; PubMed Central PMCID: PMC3390244.
  3. Maier KE, Jangra RK, Shieh KR, Cureton DK, Xiao H, Snapp EL, Whelan SP, Chandran K, Levy M. A New Transferrin Receptor Aptamer Inhibits New World Hemorrhagic Fever Mammarenavirus Entry. Mol Ther Nucleic Acids. 2016;5:e321. doi: 10.1038/mtna.2016.32; PMCID: PMCID in process.
  4. Wengerter BC, Katakowski JA, Rosenberg JM, Park CG, Almo SC, Palliser D, Levy M. Aptamer-targeted antigen delivery. Mol Ther. 2014 Jul;22(7):1375-87. PubMed PMID: 24682172; PubMed Central PMCID: PMC4089008.
  5. Kelly L, Kratschmer C, Maier KE, Yan AC, Levy M. Improved Synthesis and In Vitro Evaluation of an Aptamer Ribosomal Toxin Conjugate. Nucleic Acid Ther. 2016. doi: 10.1089/nat.2015.0599. PubMed PMID: 27228412; PubMed Central PMCID: in progress.
  6. Wilner SE, Sparks SE, Cowburn D, Girvin ME, Levy M. Controlling lipid micelle stability using oligonucleotide headgroups. J Am Chem Soc. 2015;137(6):2171-4. doi: 10.1021/ja512012m. PubMed PMID: 25634639; PMCID: PMC4861057.
  7. Katakowski JA, Mukherjee G, Wilner SE, Maier KE, Harrison MT, DiLorenzo TP, Levy M and Palliser D (2016) Delivery of siRNAs to Dendritic Cells Using DEC205-Targeted Lipid Nanoparticles to Inhibit Immune Responses. Mol Ther 24(1):146-155. PubMed PMID: 26412590; PubMed Central PMCID: PMC4754549.
  8. Padlan CS, Malashkevich VN, Almo SC, Levy M, Brenowitz M, Girvin ME. An RNA aptamer possessing a novel monovalent cation-mediated fold inhibits lysozyme catalysis by inhibiting the binding of long natural substrates. RNA. 2014 Apr;20(4):447-61. PubMed PMID: 24570482; PubMed Central PMCID: PMC3964907.

Selected Publications

Research Articles

  1. Gianella P, Snapp EL, Levy M. An in vitro compartmentalization-based method for the selection of bond-forming enzymes from large libraries. Biotechnol Bioeng. 2016;113(8):1647-57. doi: 10.1002/bit.25939. PubMed PMID: 26806853; PMCID: PMC4925268.
  2. Kelly L, Kratschmer C, Maier KE, Yan AC, Levy M. Improved Synthesis and In Vitro Evaluation of an Aptamer Ribosomal Toxin Conjugate. Nucleic Acid Therapeutics. 2016;26(3):156-65; PMCID in process
  3. Maier KE, Jangra RK, Shieh KR, Cureton DK, Xiao H, Snapp EL, Whelan SP, Chandran K, Levy M. A New Transferrin Receptor Aptamer Inhibits New World Hemorrhagic Fever Mammarenavirus Entry. Molecular Therapy—Nucleic Acids. 2016;5(5):e321; PMCID in process
  4. Katakowski JA, Mukherjee G, Wilner SE, Maier KE, Harrison T, DiLorenzi T, Levy Mand Palliser D.  Delivery of siRNAs to dendritic cells using DEC205-targeted lipid nanoparticles to inhibit immune responses. Mol Ther. 2016; Feb;24(1):146-55.
  5. Wengerter BC, Katakowski JA, Rosenberg JM, Park CG, Almo SC, Palliser D, and Levy M. Aptamer-targeted antigen delivery. Mol Ther. 2014;22(7):1375-87; PMCID: 4089008.
  6. Trevino SG, and Levy M. High-throughput bead-based identification of structure-switching aptamer beacons. Chembiochem. 2014;15(13):1877-81; PMCID: 4161366.
  7. Padlan CS, Malashkevich VN, Almo SC, Levy M, Brenowitz M, and Girvin ME. An RNA aptamer possessing a novel monovalent cation-mediated fold inhibits lysozyme catalysis by inhibiting the binding of long natural substrates. RNA. 2014;20(4):447-61; PMCID: 3964907.
  8. Lu WC, Levy M, Kincaid R, Ellington AD. Directed evolution of the substrate specificity of biotin ligase. Biotechnol Bioeng. 2014;111(6):1071-81; PMCID: in process.
  9. Wilner SE, Wengerter B, Maier K, de Lourdes Borba Magalhaes M, Del Amo DS, Pai S, Opazo F, Rizzoli SO, Yan A, and Levy M. An RNA alternative to human transferrin: a new tool for targeting human cells. Molecular therapy Nucleic acids. 2012;1:e21; PMCID: 3390244.
  10. Patel VL, Mitra S, Harris R, Buxbaum AR, Lionnet T, Brenowitz M, Girvin M, Levy M, Almo SC, and Singer RH, Chao JA. Spatial arrangement of an RNA zipcode identifies mRNAs under post-transcriptional control. Genes Dev. 2012;26(1):43-53; PMCID: 3258965.
  11. Pastore C, Topalidou I, Forouhar F, Yan AC, Levy M, Hunt JF. Crystal structure and RNA binding properties of the RNA recognition motif (RRM) and AlkB domains in human AlkB homolog 8 (ABH8), an enzyme catalyzing tRNA hypermodification. J Biol Chem. 2012;287(3):2130-43; PMCID: 3265892.
  12. Opazo F, Levy M, Byrom M, Schafer C, Geisler C, Groemer TW, Ellington AD, and Rizzoli SO. Aptamers as potential tools for super-resolution microscopy. Nat Methods. 2012;9(10):938-9; PMCID: in process.
  13. Magalhaes ML, Byrom M, Yan A, Kelly L, Li N, Furtado R, Palliser D, Ellington AD, and Levy M. A general RNA motif for cellular transfection. Mol Ther. 2012;20(3):616-24; PMCID: 3294222.
  14. Magalhaes ML, Czekster CM, Guan R, Malashkevich VN, Almo SC, and Levy M. Evolved streptavidin mutants reveal key role of loop residue in high-affinity binding. Protein Sci. 2011;20(7):1145-54; PMCID: 3149188.
  15. Soriano Del Amo D, Wang W, Jiang H, Besanceney C, Yan AC, Levy M, Liu Y, Marlow FL, and Wu P. Biocompatible copper(I) catalysts for in vivo imaging of glycans. J Am Chem Soc. 2010;132(47):16893-9; PMCID: 3021957.
  16. Davidson EA, T VANB, Levy M, and Ellington AD. Emulsion based selection of T7 promoters of varying activity. Pac Symp Biocomput. 2010:433-43; PMCID: in process.
  17. Chao JA, Patskovsky Y, Patel V, Levy M, Almo SC, and Singer RH. ZBP1 recognition of beta-actin zipcode induces RNA looping. Genes Dev. 2010;24(2):148-58; PMCID: 2807350.
  18. Narayanaswamy R, Levy M, Tsechansky M, Stovall GM, O'Connell JD, Mirrielees J, Ellington AD, and Marcotte EM. Widespread reorganization of metabolic enzymes into reversible assemblies upon nutrient starvation. Proc Natl Acad Sci U S A. 2009;106(25):10147-52; PMCID: 2691686.
  19. Hall B, Cater S, Levy M, and Ellington AD. Kinetic optimization of a protein-responsive aptamer beacon. Biotechnol Bioeng. 2009; PMCID: in process.
  20. Chen X, Denison L, Levy M, and Ellington AD. Direct selection for ribozyme cleavage activity in cells. RNA. 2009;15(11):2035-45; PMCID: 2764470.
  21. Tabor JJ, Bayer TS, Simpson ZB, Levy M, and Ellington AD. Engineering stochasticity in gene expression. Mol Biosyst. 2008;4(7):754-61; PMCID: 2630191.
  22. Levy M, and Ellington AD. Directed evolution of streptavidin variants using in vitro compartmentalization. Chem Biol. 2008;15(9):979-89; PMCID: 2615486.
  23. Javier DJ, Nitin N, Levy M, Ellington A, and Richards-Kortum R. Aptamer-targeted gold nanoparticles as molecular-specific contrast agents for reflectance imaging. Bioconjug Chem. 2008;19(6):1309-12; PMCID: 2651625.
  24. Tabor JJ, Levy M, and Ellington AD. Deoxyribozymes that recode sequence information. Nucleic Acids Res. 2006;34(8):2166-72; PMCID: 1450334.
  25. Chu TC, Twu KY, Ellington AD, and Levy M. Aptamer mediated siRNA delivery. Nucleic Acids Res. 2006;34(10):e73; PMCID: 1474074.
  26. Chu TC, Shieh F, Lavery LA, Levy M, Richards-Kortum R, Korgel BA, and Ellington AD. Labeling tumor cells with fluorescent nanocrystal-aptamer bioconjugates. Biosens Bioelectron. 2006;21(10):1859-66; PMCID: in process.
  27. Chu TC, Marks JW, 3rd, Lavery LA, Faulkner S, Rosenblum MG, Ellington AD, and Levy M. Aptamer:toxin conjugates that specifically target prostate tumor cells. Cancer Res. 2006;66(12):5989-92; PMCID: in process.
  28. Pai S, Ellington AD, and Levy M. Proximity ligation assays with peptide conjugate 'burrs' for the sensitive detection of spores. Nucleic Acids Res. 2005;33(18):e162; PMCID: 1258177.
  29. Levy M, Griswold KE, and Ellington AD. Direct selection of trans-acting ligase ribozymes by in vitro compartmentalization. RNA. 2005;11(10):1555-62; PMCID: 1370839.
  30. Levy M, Cater SF, and Ellington AD. Quantum-dot aptamer beacons for the detection of proteins. Chembiochem. 2005;6(12):2163-6; PMCID: in process.
  31. Levskaya A, Chevalier AA, Tabor JJ, Simpson ZB, Lavery LA, Levy M, Davidson EA, Scouras A, Ellington AD, Marcotte EM, and Voigt CA. Synthetic biology: engineering Escherichia coli to see light. Nature. 2005;438(7067):441-2; PMCID: in process.
  32. Collett JR, Cho EJ, Lee JF, Levy M, Hood AJ, Wan C, and Ellington AD. Functional RNA microarrays for high-throughput screening of antiprotein aptamers. Anal Biochem. 2005;338(1):113-23; PMCID: in process.
  33. Cho EJ, Yang L, Levy M, and Ellington AD. Using a deoxyribozyme ligase and rolling circle amplification to detect a non-nucleic acid analyte, ATP. J Am Chem Soc. 2005;127(7):2022-3; PMCID: in process.
  34. Levy M, and Ellington AD. Peptide-templated nucleic acid ligation. J Mol Evol. 2003;56(5):607-15; PMCID: in process.
  35. Levy M, and Ellington AD. Exponential growth by cross-catalytic cleavage of deoxyribozymogens. Proc Natl Acad Sci U S A. 2003;100(11):6416-21. doi: 10.1073/pnas.1130145100; PMCID: 164461.
  36. Miyakawa S, Cleaves HJ, Miller SL. The cold origin of life: B. Implications based on pyrimidines and purines produced from frozen ammonium cyanide solutions. Orig Life Evol Biosph. 2002;32(3):209-18; PMCID: in process.
  37. Levy M, and Ellington AD. In vitro selection of a deoxyribozyme that can utilize multiple substrates. J Mol Evol. 2002;54(2):180-90; PMCID: in process.
  38. Levy M, and Ellington AD. ATP-dependent allosteric DNA enzymes. Chem Biol. 2002;9(4):417-26; PMCID: in process.
  39. Sooter LJ, Riedel T, Davidson EA, Levy M, Cox JC, and Ellington AD. Toward automated nucleic acid enzyme selection. Biol Chem. 2001;382(9):1327-34; PMCID: in process.
  40. Nelson KE, Robertson MP, Levy M, and Miller SL. Concentration by evaporation and the prebiotic synthesis of cytosine. Orig Life Evol Biosph. 2001;31(3):221-9; PMCID: in process.
  41. Levy M, and Ellington AD. Selection of deoxyribozyme ligases that catalyze the formation of an unnatural internucleotide linkage. Bioorg Med Chem. 2001;9(10):2581-7; PMCID: in process.
  42. Nelson KE, Levy M, and Miller SL. Peptide nucleic acids rather than RNA may have been the first genetic molecule. Proc Natl Acad Sci U S A. 2000;97(8):3868-71; PMCID: 18108.
  43. Levy M, Miller SL, Brinton K, and Bada JL. Prebiotic synthesis of adenine and amino acids under Europa-like conditions. Icarus. 2000;145(2):609-13; PMCID: in process.
  44. Levy M, and Miller SL, Oro J. Production of guanine from NH(4)CN polymerizations. J Mol Evol. 1999;49(2):165-8; PMCID: in process.
  45. Levy M, and Miller SL. The prebiotic synthesis of modified purines and their potential role in the RNA world. J Mol Evol. 1999;48(6):631-7; PMCID: in process.
  46. Levy M, and Miller SL. The stability of the RNA bases: implications for the origin of life. Proc Natl Acad Sci U S A. 1998;95(14):7933-8; PMCID: 20907.
  47. Robertson MP, Levy M, and Miller SL. Prebiotic synthesis of diaminopyrimidine and thiocytosine. J Mol Evol. 1996;43(6):543-50; PMCID: in process.

 Book Chapters, Commentaries and Reviews

  1. Maier KE, Levy M. From selection hits to clinical leads: progress in aptamer discovery. Molecular therapy Methods & clinical development. 2016;5:16014.
  2. Wilner SE and Levy M. Synthesis and Characterization of Aptamer-Targeted SNALPs for the Delivery of siRNA.  Methods Mol Biol. 2016;1380:211-24.
  3. Levy M and Palliser D. Targeting Liposomes to Immune Cells. In: Biomaterials in Regenerative Medicine and the Immune System, Santambrogio L editor, Springer; 2015.
  4. Gollihar J, Levy M, and Ellington AD. Biochemistry. Many paths to the origin of life. Science. 2014 Jan 17;343(6168):259-60.
  5. Yan A, and Levy M. Cell internalization SELEX: in vitro selection for molecules that internalize into cells. Methods in molecular biology; 2014. p. 241-65.
  6. Yan AC, and Levy M. Aptamers and aptamer targeted delivery. RNA Biol; 2009. p. 316-20.
  7. Tabor JJ, Levy M, Booth Simpson Z, and Ellington AD. Parasitism and Protocells: Tragedy of the Molecular Commons. In: Rasmussen S, Bedau MA, Chen L, Deamer D, Krakauer DC, Packard NH, Stadler PF, editors. Protocells Bridging Nonliving and Living Matter. Cambridge: MIT Press; 2009. p. 367-84.
  8. Davidson EA, Dlugosz PJ, Levy M, and Ellington AD. Directed evolution of proteins in vitro using compartmentalization in emulsions.  Curr Protoc Mol Biol. 2009/07/04 ed2009. p. Unit 24 6.
  9. Sokolov K, Nida D, Descour M, Lacy A, Levy M, Hall B, Dharmawardhane S, Ellington A, Korgel B, and Richards-Kortum R. Molecular optical imaging of therapeutic targets of cancer. Adv Cancer Res. 2006/12/13 ed2007. p. 299-344.
  10. Hughes RA, Robertson MP, Ellington AD, and Levy M. The importance of prebiotic chemistry in the RNA world. Curr Opin Chem Biol. 2004/11/24 ed2004. p. 629-33.
  11. Levy M, and Ellington AD. The descent of polymerization. Nat Struct Biol. 2001/06/28 ed2001. p. 580-2.
  12. Levy M, and Ellington AD. RNA world: catalysis abets binding, but not vice versa. Curr Biol. 2001/08/30 ed2001. p. R665-7.
  13. Jasien PG, Miller SL, Levy M, and Dworkin JP. How could have life arisen on Earth? In: Lisensky G, Molinaro M, editors. Wiley Chem Connections: John Wiley & Sons; 2001.

Patents

Issued:

  1. Selection Method for Cell Internalizing Nucleic Acids, US8298764 B2, issued Oct 30, 2012.
  2. Transferrin Receptor Aptamers and Aptamer Targeted Delivery, US 9439,973 B2, issued Sept 30, 2016

 Provisional:

  1. Proximity Ligation Assays With Peptide Conjugate ‘Burrs’ For The Sensitive Detection Of Spores and Cancer Cells. (2005) U.S. Provisional Patent Application Ser. No. 60/712,600.
  2. Methods of Preparing Targeted Aptamer Prodrugs (2010) U.S. Provisional Application No. 61/395,468.
  3. Aptamer Mediated Antigen Delivery (2012) U.S. Provisional Application No. 61/671,239.
  4. Nucleic Acid-Scaffolded Small Molecule Libraries (2013) U.S. Provisional Patent App. No. 61/896,891.
  5. Method of Rapid Identification of Aptamer Beacons (2013) U.S. Provisional Patent App. No. 61/917,548.
  6. Programmed Cargo Release Using Nucleic Acid-Stabilized Micelles (2014) U.S. Provisional Patent Application No. 62/061,772
  7. Chemically Modified RNA Aptamers and Uses Thereof (2016) U.S. Provisional Patent App. No. 62/408,859