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 #
5P01HL051811-18
Application #
8126377
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
2011-05-01
Budget End
2012-04-30
Support Year
18
Fiscal Year
2011
Total Cost
$1,139,310
Indirect Cost
Name
Johns Hopkins University
Department
Physiology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Kates, Max; Date, Abhijit; Yoshida, Takahiro et al. (2017) Preclinical Evaluation of Intravesical Cisplatin Nanoparticles for Non-Muscle-Invasive Bladder Cancer. Clin Cancer Res 23:6592-6601
Guggino, William B; Benson, Janet; Seagrave, JeanClare et al. (2017) A Preclinical Study in Rhesus Macaques for Cystic Fibrosis to Assess Gene Transfer and Transduction by AAV1 and AAV5 with a Dual-Luciferase Reporter System. Hum Gene Ther Clin Dev 28:145-156
Schuster, Benjamin S; Allan, Daniel B; Kays, Joshua C et al. (2017) Photoactivatable fluorescent probes reveal heterogeneous nanoparticle permeation through biological gels at multiple scales. J Control Release 260:124-133
Schneider, Craig S; Xu, Qingguo; Boylan, Nicholas J et al. (2017) Nanoparticles that do not adhere to mucus provide uniform and long-lasting drug delivery to airways following inhalation. Sci Adv 3:e1601556
Duncan, Gregg A; Jung, James; Joseph, Andrea et al. (2016) Microstructural alterations of sputum in cystic fibrosis lung disease. JCI Insight 1:e88198
Yu, Tao; Chisholm, Jane; Choi, Woo Jin et al. (2016) Mucus-Penetrating Nanosuspensions for Enhanced Delivery of Poorly Soluble Drugs to Mucosal Surfaces. Adv Healthc Mater 5:2745-2750
Schuster, Benjamin S; Ensign, Laura M; Allan, Daniel B et al. (2015) Particle tracking in drug and gene delivery research: State-of-the-art applications and methods. Adv Drug Deliv Rev 91:70-91
Mastorakos, Panagiotis; da Silva, Adriana L; Chisholm, Jane et al. (2015) Highly compacted biodegradable DNA nanoparticles capable of overcoming the mucus barrier for inhaled lung gene therapy. Proc Natl Acad Sci U S A 112:8720-5
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
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

Showing the most recent 10 out of 123 publications