It is overall goal of this Center to utilize the strengths of our current CF Research Group in basic and clinical research and patient care to develop gene and pharmacologic therapies for patients with CF.
The specific aims are to develop adeno-associated viral vectors as gene therapy agents and to explore new pharmacologic therapies based upon altering expression and trafficking of mutant CFTR. Project 1 will develop a new AAV gene therapy vector based on the AAV5 serotype as a new therapy for CF.
The aims will be to: assess the efficiency and distribution of vector DNA transfer and to determine the risk of immunologic reactions, alterations in pulmonary function, or spread in distant organs in monkeys. This will be followed by a clinical trial in adult CF patients. Project II: Adeno-associated virus vectors for CF gene therapy. The primary hypotheses to be tested ti that: Aberrant down-regulation of certain anti-protease, anti-inflammatory, and glycosylation-related genes contribute to CF lung disease, and augmentation of these substances will ameliorate the CF lung disease phenotype. Project III: Phenylbutyrate Therapy for CF is based on the hypothesis that phenylbutyrate can act to partially correct defective nasal potential difference in CF patients. The goals are to pinpoint exactly how phenylbutyrate functions to partially restore transport function. Project IV will focus on the Biology of AAV. Finally, there are three cores, an Expression, a Vector Core, and an Administration Core.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL051811-20
Application #
8479396
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Program Officer
Banks-Schlegel, Susan P
Project Start
1997-09-01
Project End
2014-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
20
Fiscal Year
2013
Total Cost
$1,056,163
Indirect Cost
$281,578
Name
Johns Hopkins University
Department
Physiology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
da Silva, Adriana L; Martini, Sabrina V; Abreu, Soraia C et al. (2014) DNA nanoparticle-mediated thymulin gene therapy prevents airway remodeling in experimental allergic asthma. J Control Release 180:125-33
Smith, Laura J; Ul-Hasan, Taihra; Carvaines, Sarah K et al. (2014) Gene transfer properties and structural modeling of human stem cell-derived AAV. Mol Ther 22:1625-34
Schuster, Benjamin S; Kim, Anthony J; Kays, Joshua C et al. (2014) Overcoming the cystic fibrosis sputum barrier to leading adeno-associated virus gene therapy vectors. Mol Ther 22:1484-93
Salganik, Maxim; Aydemir, Fikret; Nam, Hyun-Joo et al. (2014) Adeno-associated virus capsid proteins may play a role in transcription and second-strand synthesis of recombinant genomes. J Virol 88:1071-9
Suk, Jung Soo; Kim, Anthony J; Trehan, Kanika et al. (2014) Lung gene therapy with highly compacted DNA nanoparticles that overcome the mucus barrier. J Control Release 178:8-17
Birket, Susan E; Chu, Kengyeh K; Liu, Linbo et al. (2014) A functional anatomic defect of the cystic fibrosis airway. Am J Respir Crit Care Med 190:421-32
Schuster, Benjamin S; Suk, Jung Soo; Woodworth, Graeme F et al. (2013) Nanoparticle diffusion in respiratory mucus from humans without lung disease. Biomaterials 34:3439-46
Govindasamy, Lakshmanan; DiMattia, Michael A; Gurda, Brittney L et al. (2013) Structural insights into adeno-associated virus serotype 5. J Virol 87:11187-99
Cebotaru, Liudmila; Woodward, Owen; Cebotaru, Valeriu et al. (2013) Transcomplementation by a truncation mutant of cystic fibrosis transmembrane conductance regulator (CFTR) enhances ?F508 processing through a biomolecular interaction. J Biol Chem 288:10505-12
Kim, Anthony J; Boylan, Nicholas J; Suk, Jung Soo et al. (2012) Non-degradative intracellular trafficking of highly compacted polymeric DNA nanoparticles. J Control Release 158:102-7

Showing the most recent 10 out of 106 publications