... 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 genetherapy ... 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 ingenetherapy can clearly be found both within the CF field and in parallel areas...
... 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 cysticfibrosis 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...
... 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...
... of HSC can provide for the continuous maintenance of the transgene in cells of hematopoetic origin, including red blood cells, platelets, neutrophils, and 138 GENETHERAPYFOR HEMATOLOGICAL DISORDERS ... CELLS AS TARGETS FORGENETHERAPY 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...
... AAV ingenetherapy 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 GENETHERAPY VIRAL VECTORS USED FORGENETHERAPY Based on the virus life cycle, infectious virions are very efficient at transferring genetic information Most genetherapy experiments...
... abilities Forin vivo gene therapy, the therapeutic or normal gene is introduced directly into the host On one hand, in vivo genetherapy 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, genetherapy can be accomplished to correct genetic defects by in vivo methods Ideally, a vehicle forin vivo genetherapyfor the...
... sCD4 for the genetherapy 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 GENETHERAPY 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...
... and overcome, rAAV-based gene transfer vectors still represent one of the most promising genetherapy 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 ingenetherapy applications, ... isolation, as well as methods forgene transfer and expression inin vitro studies As this vector system was used with increasing ingene delivery protocols, the interest in the complexities of AAV...
... and overcome, rAAV-based gene transfer vectors still represent one of the most promising genetherapy 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 ingenetherapy applications, ... isolation, as well as methods forgene transfer and expression inin vitro studies As this vector system was used with increasing ingene delivery protocols, the interest in the complexities of AAV...
... advantageous for choosing a target forgenetherapyIn 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 inGeneTherapy Fig Finding Novel GeneTherapy Targets Integration of standard and modern technologies for disease-causing targets forgene ... targets and also focus on choosing newer targets forgenetherapy Known targets forgenetherapy The general aim of genetherapy is to introduce a well-defined DNA sequence into specific cells Almost...
... 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...
... 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 incysticfibrosis and non -cystic fibrosis airway epithelial cells J Immunol 2005, 174:1638-1646...
... patients with cysticfibrosis as recently reported for Inquilinus limosus [2] The increased clinical use of nebulized colistin in patients with cysticfibrosis 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...
... Koch C: Cysticfibrosis Pseudomonas aeruginosa infection incysticfibrosis and its management Thorax 1990, 45(11):881-4 Bals R, Weiner DJ, Wilson JM: The innate immune system incysticfibrosis ... 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 incysticfibrosis 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...
... Setoguchi Y, Takahashi H, Tomino Y, Koide H: Genetherapyfor 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 ingenetherapy ... Genetic Vaccines and Therapy 2008, 6:10 Background Therapeutic protein secretion by an in vivo transfected organ is one of the major genetherapy applications One drawback to be avoided in...
... Hypertonic Saline inCysticFibrosis (NHSCF) Study Group A controlled trial of long-term inhaled hypertonic saline in patients with cysticfibrosis 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...
... transgene expression in the joint was high [48], but interestingly the transgene expression also increased with joint inflammation [49] Clinical efficacy of local genetherapy with recombinant ... thus the former is the vector of choice for future genetherapy trials The number of genetherapy trials in RA is in sharp contrast to the more than 600 clinical trials of genetherapyin 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...
... 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...