challenges in gene therapy for cystic fibrosis

... changes in clinical endpoints, including circulating levels of factor IX and the frequency of infusion of factor IX protein The questions that remain to be answered for successful CF gene therapy ... UTP-binding P2Y2 receptor Novel viruses are increasingly being investigated, and cationic liposomes and polymers are increasingly being coupled to peptides, sugars and viral particles to try to increase ... unglamorous effort needs to be expended to move from proof of principle to clinical product Encouraging progress in gene therapy can clearly be found both within the CF field and in parallel areas...

Ngày tải lên: 12/08/2014, 18:20

... significantly from the HardyWeinberg equilibrium indicating no bias in sampling in Table 2: Genotype frequencies and p-value for Hardy-Weinberg equilibrium (HWE) in the cystic fibrosis patients The genotype ... sensitivity in a tissue-specific manner As the inflammatory process in CF is dominated by a neutrophil influx in the airways, our present findings reporting that CF patients carrying the BclI ... and OT have been involved in the interpretation of the data AH-C has been involved in collecting the patients DNA and the phenotypical data BF and JF have been involved in revisiting the manuscript...

Ngày tải lên: 12/08/2014, 15:21

... periodic intrahepatic injections of purified cPMP from Escherichia coli [8] to achieve a suitable size for tail vein injection Intrahepatic injections were done every other day with increasing amounts ... after either intrahepatic or intravenous injection [5] Using the MOCS1 expression cassette in an AAV 1/2 capsid, we here studied the effect of systemic delivery by tail vein injections For this application ... encoding the green fluorescent protein (AAV-EGFP) on day after birth The EGFP expression cassette contains the coding sequence for EGFP instead of the MOCS1 cDNA Recombinant viruses were generated...

Ngày tải lên: 14/08/2014, 19:22

... of HSC can provide for the continuous maintenance of the transgene in cells of hematopoetic origin, including red blood cells, platelets, neutrophils, and 138 GENE THERAPY FOR HEMATOLOGICAL DISORDERS ... CELLS AS TARGETS FOR GENE THERAPY 139 include the combination of interleukin (IL-3), interleukin (IL-6), and stem cell factor (SCF) Inclusion of recently discovered early acting growth factors ... same gene- modified cell population in both patients and immunodeficient mice Clinical Genetic Marking Studies Genetic marking of cells with an integrating vector is a unique method for tracking...

Ngày tải lên: 10/04/2014, 22:10

... AAV in gene therapy is the ability to transfer genetic information into nondividing cells in vivo In addition, expression has been maintain for up to one year Further experiments to determine ... promotor, resulting in tatindependent transcription The self-inactivating vector was constructed by deleting 133 bp in the U3 region of the 3¢ LTR including the TATA box and the binding sites for specific ... 78 VECTORS OF GENE THERAPY VIRAL VECTORS USED FOR GENE THERAPY Based on the virus life cycle, infectious virions are very efficient at transferring genetic information Most gene therapy experiments...

Ngày tải lên: 10/04/2014, 22:11

... abilities For in vivo gene therapy, the therapeutic or normal gene is introduced directly into the host On one hand, in vivo gene therapy circumvents the need for the invasive procedures of harvesting ... response against the malignant cells through the introduction of genes coding for a cytokine Alternatively, the “suicide -gene approach, in which a gene, coding for an enzyme, is introduced into tumor ... human AAT gene into dogs using the ex vivo method Ideally, however, gene therapy can be accomplished to correct genetic defects by in vivo methods Ideally, a vehicle for in vivo gene therapy for the...

Ngày tải lên: 10/04/2014, 22:11

... sCD4 for the gene therapy of HIV infection in a clinical setting has been disappointing The intravenous infusion of recombinant sCD4 protein in HIV-infected patients failed to show efficacy in phase ... administering increasing doses of autologous CD8+ class I ANTI-HIV GENE THERAPY CLINICAL TRIALS TABLE 11.2 283 Clinical Trials for HIV-1 Protocol Description Status Investigator Institute Gene ... viral proteins in the ER by specific interaction with the BiP protein by inducing or repressing cellular factors that in turn in uence viral gene expression One of the most successful in vitro uses...

Ngày tải lên: 10/04/2014, 22:11

... and overcome, rAAV-based gene transfer vectors still represent one of the most promising gene therapy systems and gain increasing popularity In a search for "AAV gene therapy" , 1,016 PubMed references ... foundation of recombinant AAV vectors capable of expressing foreign genes in mammalian cells [8,9], in the early 1980s, AAV2 vectors have rapidly gained popularity in gene therapy applications, ... isolation, as well as methods for gene transfer and expression in in vitro studies As this vector system was used with increasing in gene delivery protocols, the interest in the complexities of AAV...

Ngày tải lên: 18/06/2014, 18:20

... and overcome, rAAV-based gene transfer vectors still represent one of the most promising gene therapy systems and gain increasing popularity In a search for "AAV gene therapy" , 1,016 PubMed references ... foundation of recombinant AAV vectors capable of expressing foreign genes in mammalian cells [8,9], in the early 1980s, AAV2 vectors have rapidly gained popularity in gene therapy applications, ... isolation, as well as methods for gene transfer and expression in in vitro studies As this vector system was used with increasing in gene delivery protocols, the interest in the complexities of AAV...

Ngày tải lên: 20/06/2014, 01:20

... advantageous for choosing a target for gene therapy In addition, the execution of therapy is more straightforward, since it is easier to transfer single genes into cells instead of several genes Other ... future for new gene therapeutics shows promise 10 Targets in Gene Therapy Fig Finding Novel Gene Therapy Targets Integration of standard and modern technologies for disease-causing targets for gene ... targets and also focus on choosing newer targets for gene therapy Known targets for gene therapy The general aim of gene therapy is to introduce a well-defined DNA sequence into specific cells Almost...

Ngày tải lên: 28/06/2014, 05:20

... taken into account by a pencil beam algorithm Dose constraints for the spinal cord were set at 45 Gy, V20 (volume receiving >20 Gy) for a single lung at 50%, V25 for both lungs considered as a single ... patients With ongoing practice some 'rules' evolved, breaking some former "taboos" in radiotherapy of lung cancer: Minimizing the dose to the ipsilateral (i.e tumor bearing) lung In many cases the ... Shortly, slow planning CTs depict the different relevant positions of the moving tumors individually, so that adding a general extra-margin for tumor motion (internal margin) is not necessary...

Ngày tải lên: 09/08/2014, 10:20

... Musculoskeletal manifestations in cystic fibrosis Joint Bone Spine 2003, 70:327-335 Festini F, Ballarin S, Codamo T, Doro R, Loganes C: Prevalence of pain in adults with cystic fibrosis J Cyst Fibros ... Lewiston N: Back pain and spinal deformity in cystic fibrosis Arch Ped Adol Med 1987, 141:1313-1316 Conwell LS, Chang AB: Bisphosphonates for osteoporosis in people with cystic fibrosis Cochrane ... Sauer-Heilborn A, Köhnlein T, Seidler U, Lamprecht G: Cystic fibrosis in adults Internist 2010, 51(Suppl 1):277-288 Ravilly S, Robinson W, Suresh S, Wohl ME, Berde CB: Chronic pain in cystic fibrosis Pediatrics...

Ngày tải lên: 10/08/2014, 23:20

... transfected into HEK293 cells using Fugene HD (Roche Diagnostics, Indianapolis, IN) Clonal cell-lines stably expressing the construct were identified following selection in Hygromycin-containing media ... is relevant to airway inflammation noted in patients [14,15] Inflammation in CF is caused by a complex mixture of bacterial products including secreted toxins, lipoproteins, lipopolysaccharides ... Carroll TP, Smith SG, Taggart CC, Devaney J, Griffin S, O'Neill SJ, McElvaney NG: TLR-induced inflammation in cystic fibrosis and non -cystic fibrosis airway epithelial cells J Immunol 2005, 174:1638-1646...

Ngày tải lên: 11/08/2014, 08:22

... patients with cystic fibrosis as recently reported for Inquilinus limosus [2] The increased clinical use of nebulized colistin in patients with cystic fibrosis may select specific colistin-resistant ... immunocompromised hosts including bacteraemia, urinary infection and emphysema [5,6] In a study by Kiska et al [3], B diminuta was isolated in a patient with cystic fibrosis, after being misidentified ... trimethoprim/sulphamethoxazole and colistin but remained susceptible to ceftriaxone, ticarcillin, ticarcillin/ clavulanic acid, imipenem, amikacin, tobramycin, gentamicin, isepamicin, rifampicin, and piperacillin/tazobactam...

Ngày tải lên: 11/08/2014, 19:21

Ngày tải lên: 12/08/2014, 04:21

... Koch C: Cystic fibrosis Pseudomonas aeruginosa infection in cystic fibrosis and its management Thorax 1990, 45(11):881-4 Bals R, Weiner DJ, Wilson JM: The innate immune system in cystic fibrosis ... reasons, inherent to the determination of cytokine protein levels in induced sputum supernatants including the use of DTT to process the samples and the dilution factor Therefore, we could not perform ... Th1/Th2 cytokine response in cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection APMIS 2005, 113(6):400-9 Lankford CS, Frucht DM: A unique role for IL-23 in promoting cellular...

Ngày tải lên: 12/08/2014, 13:22

... Setoguchi Y, Takahashi H, Tomino Y, Koide H: Gene therapy for renal anemia in mice with polycystic kidney using an adenovirus vector encoding the human erythropoietin gene Kidney Int 1999, 55(4):1234-1240 ... Therefore, in the particular case of Epo, an accurate level of transgene expression is required for safety reasons Temporal control systems of transgene expression have already been used in gene therapy ... Genetic Vaccines and Therapy 2008, 6:10 Background Therapeutic protein secretion by an in vivo transfected organ is one of the major gene therapy applications One drawback to be avoided in...

Ngày tải lên: 14/08/2014, 19:22

... Hypertonic Saline in Cystic Fibrosis (NHSCF) Study Group A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis N Engl J Med 2006; 354: 229-240 Robinson M, Daviskas ... fucose/galacatose to other inhalations (eg hypertonic saline) In conclusion the findings in this report show that inhalation with fucose/galactose solution could reduce P aeruginosa in sputum of adult ... combined therapy (P > 0.05) In peripheral blood inhalation alone and combined therapy did not significantly alter the numbers or precentages of PBMC (P > 0.05) TABLE 2: Inflammatory cells in sputum...

Ngày tải lên: 03/11/2012, 11:48

... transgene expression in the joint was high [48], but interestingly the transgene expression also increased with joint inflammation [49] Clinical efficacy of local gene therapy with recombinant ... thus the former is the vector of choice for future gene therapy trials The number of gene therapy trials in RA is in sharp contrast to the more than 600 clinical trials of gene therapy in patients ... activity in murine collagen-induced arthritis Gene Ther 2003, 10:19501960 Yin G, Liu W, An P, Li P, Ding I, Planelles V, Schwarz EM, Min W: Endostatin gene transfer inhibits joint angiogenesis...

Ngày tải lên: 09/08/2014, 01:24

... pulses) on ice in cold room using the T-PER (Pierce Biotech Inc., Rockford, IL) protein lysis buffer containing protease-inhibitor cocktail (Pierce) The protein extracts were suspended in Laemmli’s ... with PLGA nanoparticles using ring-opening polymerization method, results in increased residence in blood (intravenous) or airway (intranasal) and enhanced accumulation in target tissues or cells ... sustained release and delivery of FDA approved proteasome inhibitor drug, PS341 in murine lungs by its ability to control Pseudomonas aeruginosa LPS induced CF lung disease in murine model In this...

Ngày tải lên: 11/08/2014, 00:22