Copernicus Therapeutics Inc.

Nucleic Acid Nanoparticles for Treating Human Diseases



Harmon BT, Aly AE, Padegimas L, Sesenoglu-Laird O, Cooper MJ, Waszcak BL. Intranasal administration of plasmid DNA nanoparticles yields successful transfection and expression of reporter protein in rat brain. Gene Ther. 2014 Mar 27. doi: 10.1038/gt.2014.28 [Epub ahead of print]
PMID: 24670994

Koirala A, Conley SM, Makkia RS,  Liu Z, Cooper MJ, Sparrow JR, Naash MI. Persistence of non-viral vector mediated RPE65 expression: Case for viability as a gene transfer therapy for RPE-based diseases. J Control Release. 172(3):745-52, 2013. PMID: 24035979

Koirala A, Makkia RS, Conley SM, Cooper MJ, Naash MI. S/MAR-containing DNA nanoparticles promote persistent RPE gene expression and improvement in RPE65 LCA. Hum Mol Genet, 22(8):1632-1642, 2013. PMID: 23335596

Han Z, Conley SM, Makkia RS, Cooper MJ, Naash MI. Nanoparticle-mediated ABCA4 delivery rescues the degenerative Stargardt’s phenotype. J Clin Investigation, 122(9):3221-3226, 2012.

PMID: 22886305

Han Z, Makkia RS, Conley SM, Guo J, Cooper MJ, Naash MI. Comparative Analysis of DNA Nanoparticles and AAVs for Ocular Gene Delivery. PloS One, 7(12):e52189, 2012. PMID: 23272225


Han Z, Koirala A, Makkia RS, Cooper MJ, Naash MI. Direct gene transfer with compacted DNA nanoparticles in retinal pigment epithelial cells: expression, repeat delivery and lack of toxicity. Nanomedicine, 7(4):521-539, 2012. PMID: 22356602


Boylan NJ, Kim AJ, Suk JS, Adstamongkonkul P, Simons BW, Lai SK, Cooper MJ, Hanes J. A new pH-responsive polymer enhances airway gene transfer by highly compacted DNA nanoparticles. Biomaterials, 33:2361-2371, 2012. PMID:22182747


Boylan NJ, Suk JS, Lai SK, Jelinek R, Boyle MP, Cooper MJ, Hanes J. Highly compacted DNA nanoparticles with low MW PEG coatings: in vitro, ex vivo and in vivo evaluation.  J Controlled Release, 157:72-79, 2012PMID: 21903145


Padegimas L, Kowalczyk TH, Adams S, Gedeon CR, Oette SM, Dines K, Hyatt SL, Sesenoglu-Laird O, Tyr E, Moen RC,  Cooper MJ. Optimization of hCFTR lung expression in mice using DNA nanoparticles. Mol Ther, 20:63-72, 2012. PMID: 21952168


Koirala A, Makkia RS, Cooper MJ, Naash MI. Nanoparticle-mediated gene transfer specific to retinal pigment epithelial cells. Biomaterials, 32(35):9483-9493, 2011. PMID: 21885113


Suk JS, Boylan NJ, Trehan K, Tang BC, Schneider CS, Lin JM, Boyle MP, Zeitlin PL, Lai SK, Cooper MJ, Hanes J. N-acetylcysteine enhances cystic fibrosis sputum penetration and airway gene transfer by highly compacted DNA nanoparticles. Mol Ther, 19(11):1981-1989, 2011. PMID: 21829177


Fletcher AM, Kowalczyk TH, Padegimas L, Cooper MJ, Yurek DM. Transgene expression in the striatum following intracerebral injections of DNA nanoparticles encoding for human glial cell line-derived neurotrophic factor (hGDNF). Neuroscience, 194:220-226, 2011. PMID: 21839809


Yurek DM, Fletcher AM, McShane M, Kowalczyk TH, Padegimas L, Weatherspoon MR, Kaytor MD, Cooper MJ, Ziady AG. DNA nanoparticles: detection of long-term transgene activity in brain using bioluminescence imaging (BLI). Mol Imaging, 10(5):327-339, 2011. PMID: 21521549

Cai X, Conley SM, Nash Z, Fliesler SJ, Cooper MJ, Naash MI. Gene delivery to mitotic and postmitotic photoreceptors via compacted DNA nanoparticles provides improved phenotype in a mouse model of retinitis pigmentosa. FASEB J, 24(4):1178-1191, 2010. PMID: 19952284


Ding X-Q, Quiambao AB, Fitzgerald JB, Cooper MJ, Conley SM, Naash MI. Ocular delivery of compacted DNA-nanoparticles does not elicit toxicity in the mouse retina. PloS One, 4(10): e7410, 2009.

PMID: 19823583


Yurek DM, Fletcher AM, Kowalczyk TH, Padegimas L, Cooper MJ. Compacted DNA nanoparticle gene transfer of GDNF to the rat striatum enhances the survival of grafted fetal dopamine neurons. Cell Transplantation. 18:1183-1196, 2009. PMID: 19650971


Cai X, Nash Z, Conley SM, Fliesler SJ, Cooper MJ, Naash MI. A partial structural and functional rescue of a retinitis pigmentosa model with compacted DNA nanoparticles. PloS One, 4(4):e5290, 2009. PMID: 19390689


Yurek DM, Fletcher AM, Smith GM, Seroogy KB, Ziady AG, Molter J, Kowalczyk TH, Padegimas L,  Cooper MJ. Long-term transgene expression in the central nervous system using DNA nanoparticles. Mol Ther, 17(4):641-650, 2009. PMID: 19223866


Chen X, Kube DM, Cooper MJ, Davis PB. Cell surface nucleolin serves as receptor for DNA nanoparticles composed of PEGylated polylysine and DNA. Mol Ther. 16(2):333-342, 2008.

PMID: 18059369


Davis PB, Cooper MJ. Vectors for airway gene delivery.  AAPS Journal, 9(1):E11-17, 2007.

PMID: 17408235


Farjo R, Skaggs J, Quiambao AB, Cooper MJ, Naash MI. Efficient non-viral ocular gene transfer with compacted DNA nanoparticles. PLoS One, 10.1371/journal.pone.0000038, 2006. PMID: 17183666


Fink TL, Klepcyk PJ, Oette SM, Gedeon CR, Hyatt SL, Kowalczyk TH, Moen RC, Cooper, MJ. Plasmid size up to 20 kbp does not limit effective in vivo lung gene transfer using compacted DNA nanoparticles. Gene Ther, 13:1048-1051, 2006. PMID: 16525478


Davis PB.Cystic fibrosis since 1938. Am. J. Respir. Crit. Care Med., 173(5):475-82, 2006.

PMID: 16126935


Kube DM., Fletcher D, Davis PD. Relation of exaggerated cytokine responses of CF airway epithelial cells to PAO1 adherence. Respir. Res., 6(1):69, 2005. PMID: 16008840


Gupta S, Heacock M, Perez A, Davis PB. Antibodies to the polymeric immunoglobulin receptor with different binding and trafficking patterns. Am. J. Respir. Cell Mol. Biol., 33(4):363-70, 2005.

PMID: 15994431


Davis PB, Drumm ML. Some like it hot: curcumin and CFTR. Trends Mol. Med., (10):473-475, 2004. PMID: 15464445


Davis PB, Schluchter MD, Konstan MWRelation of sweat chloride concentration to severity of lung disease in cystic fibrosis. Pediatr. Pulmonol., 38(3):204-209, 2004. PMID: 15274098


van Heeckeren AM, Scaria A, Schluchter MD, Ferkol TW, Wadsworth S, Davis PB. Delivery of CFTR by adenoviral vector to cystic fibrosis mouse lung in a model of chronic Pseudomonas aeruginosa lung infection. Am. J. Physiol. Cell Mol. Physiol., 286(4):L717-726, 2004. PMID: 14514520


Perez A, Davis PB. Gene profile changes after Pseudomonas aeruginosa exposure in immortalized airway epithelial cells. J. Struct. Funct. Genomics, 5(3):179-194, 2004. PMID: 15263834


van Heeckeren AM, Schluchter MD, Zue L, Alvarez J, Freedman S, St George J, Davis PB. Nutritional effects on host response to lung infections with mucoid Pseudomonas aeruginosa in mice. Infect. Immun., 72(3):1479-1486, 2004. PMID: 14977953


Ziady AG, Kim J, Colla J, Davis PB.Defining strategies to extend duration of gene expression from targeted compacted DNA vectors. Gene Therapy, 11(18):1378-1390, 2004. PMID: 15269710


Konstan MW, Davis PB, Wagener JS, Hilliard KA, Stern RC, Milgram LJH, Kowalczyk TH, Hyatt SL, Fink TL, Gedeon CR, Oette SM, Payne JM, Muhammad O, Ziady AG, Moen RC, Cooper MJ. Compacted DNA nanoparticles administered to the nasal mucosa of cystic fibrosis subjects are safe and demonstrate partial to complete CFTR reconstitution. Human Gene Ther, 15:1255-1269, 2004.

PMID: 15684701


van Heeckeren AM, Schluchter MD, Drumm ML, Davis PB. Role of CFTR genotype in the response to chronic Pseudomonas aeruginosa lung infection in mice. Am. J. Physiol. Lung Cell. Mol. Physiol., 287(5): L944-952, 2004. PMID: 15246977


Gupta S, Zie J, Ma J, Davis PB.Intermolecular interaction between R domains of cystic fibrosis transmembrane conductance regulator. Am. J. Respir. Cell Mol. Biol.,(30)2:242-248, 2003.

PMID: 12933354


Chmiel JF, Davis PB. State of the art: why do the lungs of patients with cystic fibrosis become infected and why can’t they clear the infection? Respir. Res., 4(1):8, 2003. PMID: 14511398


Ziady AG, Gedeon CR, Miller T, Quan W, Payne JM, Hyatt SL, Fink TL, Muhammad O, Oette S, Kowalczyk T, Pasumarthy MK, Moen RC, Cooper MJ, Davis PB. Transfection of airway epithelium by stable PEGylated poly-L-lysine DNA nanoparticles In Vivo.  Mol Ther, 8:936-947, 2003.

PMID: 14664796


Ziady AG, Gedeon CR, Muhammad O, Oette SM, Fink TL, Quan W, Kowalczyk TH, Hyatt SL, Peischl A, Seng JE, Moen RC, Cooper MJ, Davis PB. Minimal toxicity of stabilized compacted DNA nanoparticles in the murine lung.  Mol Ther, 8:948-956, 2003. PMID: 14664797


Liu G, Li D, Pasumarthy MK, Kowalczyk TH, Gedeon C, Hyatt S,Payne JM, Miller TJ, Brunovskis P, Moen RC, Hanson RW, Cooper MJ. Nanoparticles of compacted DNA transfect post-mitotic cells.  J Biol Chem 278:32578-32586, 2003. PMID: 12807905

Meilander NJ, Pasumarthy MK, Kowalczyk TH, Cooper MJ, Bellamkonda RV. Sustained release of plasmid DNA using lipid microtubules and agarose hydrogel. J.Controlled Release, 88:321-331, 2003. PMID: 12628338


Ziady AG, Davis PB, Konstan MW. Non-viral gene transfer therapy for cystic fibrosis. Expert Opin. Biol. Ther., 3(3):449-58, 2003. PMID: 12783613


Ferkol T, Cohn LA, Phillips TE, Smith A, Davis PB. Targeted delivery of antiprotease to the epithelial surface of human tracheal xenografts. Am. J. Respir. Crit. Care Med., 167(10):1374-1379, 2003.

PMID: 12615618


Ziady AG, Davis PB. Receptor-directed molecular conjugates for gene transfer. Methods Mol. Med., 69:25-48, 2002. PMID: 11987782


Ziady AG, Kelley TJ, Milliken E, Ferkol T, Davis PB. Functional evidence of CFTR gene transfer in nasal epithelium of cystic fibrosis mice in vivo following luminal application of DNA complexes targeted to the serpin-enzyme complex receptor. Mol. Ther. 5(4):413-419, 2002. PMID: 11945068


Gupta S, Eastman J, Silski C, Ferkol T, Davis PB. Single chain Fv: a ligand in receptor-mediated gene delivery. Gene Ther., 8(8):586-592, 2001. PMID: 11320404


Liu G, Molas M, Grossman GA, Pasumarthy M, Perales JC, Cooper MJ, Hanson RW. Biological properties of poly-L-lysine-DNA complexes generated by cooperative binding of the polycation. J. Biol. Chem.; 276:34379-34387, 2001. PMID: 11438546


Eckman EA, Mallender WD, Szegletes T, Silski CL, Schreiber JR, Davis PB, Ferkol TW. In vitro transport of active 1-antitrypsin to the apical surface of epithelia by targeting the polymeric immunoglobulin receptor. Am. J. Respir. Cell Mol. Biol.,21:246-252, 1999. PMID: 10423408


Ziady AG, Ferkol T, Dawson DV, Perlmutter DH, Davis PB. Chain length of the polylysine in receptor-targeted gene transfer complexes affects duration of reporter gene expression both in vitro and in vivo. J. Biol. Chem., 274:4908-4916, 1999. PMID: 9988733


Ziady AG, Ferkol T, Gerken T, Dawson DV, Perlmutter DH, Davis PB. Ligand substitution of receptor targeted DNA complexes affects gene transfer into hepatoma cells. Gene Ther., 5:1685-1697, 1998. PMID: 10023448

Ferkol T, Mularo F, Hilliard J, Lodish S, Perales JC, Ziady AG, Konstan M. Transfer of the human 1-antitrypsin gene into pulmonary macrophages in vivo. Am.J. Respir. Cell Mol. Biol., 18:591-601, 1998. PMID: 9569229


Ziady AG, Perales JC, Ferkol T, Gerken T, Beegen H, Perlmutter DH, Davis PB. Gene transfer into hepatoma cell lines via the serpin enzyme complex receptor. Am. J. Physio. 273:G545-G552, 1997. PMID: 9277436


Perales JC, Grossmann GA, Molas M, Lie G, Ferkol T, Harpst J, Oda H, Hanson RW. Biochemical and functional characterization of DNA complexes capable of targeting genes to hepatocytes via the asialoglycoprotein receptor. J.Biol. Chem., 272(11):7398-7407, 1997. PMID: 9054440


Garcia-Valenzuela E, Perales JC, Hanson RW, Sharma SC. Axon-mediated gene transfer of retinal ganglion cells in vivo. J. Neurobiol, 32(1):111-122, 1997. PMID: 8989667


Cooper MJ, Lippa M, Payne JM, Hatzivassiliou G, Reifenberg E, Fayazi B, Perales J, Morrison LJ, Templeton D, Pickarz RL, Tan J. Safety-modified episomal vectors for human gene therapy.  Proc Natl Acad Sci USA 94:6450-6455, 1997. PMID: 9177238


Ferkol T, Perales JC, Mularo F, Hanson RW Receptor-mediated gene transfer into macrophages. Proc. Nat. Acad. Sci., 93:101-105, 1996. PMID: 8552583


Ferkol T, Pellicina-Palle A, Eckman E, Perales JC, Trzaska T, Tosi M, Redline R, Davis PB. Immunologic responses to gene transfer into mice via the polymeric immunoglobulin receptor. Gene Ther., 3(8):669-678, 1996. PMID: 8854092


Cooper MJ. Non-infectious gene transfer and expression systems for cancer gene therapy. Semin. Oncol. 23(1):172-187, 1996. PMID: 8607027


Ferkol T, Perales JC, Eckman E, Kaetzel CS, Hanson RW, Davis PB. Gene transfer into the airway epithelium of animals by targeting the polymeric immunoglobulin receptor. J. Clin. Invest., 95(2):493-502, 1995. PMID: 7860731


Perales JC, Ferkol T, Molas M, Hanson RW. An evaluation of receptor-mediated gene transfer using synthetic DNA-ligand complexes. Eur. J. Biochem., 226(2):255-266, 1994. PMID: 8001543


Perales JC, Ferkol T, Beegen H, Ratnoff OD, Hanson RW. Gene transfer in vivo: Sustained expression and regulation of genes introduced into the liver by receptor-targeted uptake. Proc. Nat. Acad. Sci., 91(9):4086-4090, 1994. PMID: 8171039