|
Hemophilia B
|
0.090 |
GeneticVariation
|
disease |
BEFREE |
Recent hemophilia B clinical trials using adeno-associated virus (AAV) gene delivery have demonstrated much lower coagulation factor IX (FIX) production in patients compared with the high levels observed in animal models and AAV capsid-specific cytotoxic T lymphocyte response elicited at high doses of AAV vectors.
|
27834949 |
2017 |
|
Hemophilia B
|
0.090 |
GeneticVariation
|
disease |
BEFREE |
Multiple independent adeno-associated virus (AAV) gene therapy clinical trials for hemophilia B, utilizing different AAV serotypes, have reported a vector dose-dependent loss of circulating factor IX (FIX) protein associated with capsid-specific CD8<sup>+</sup> T cell (Cap-CD8) elimination of transduced hepatocytes.
|
28480313 |
2017 |
|
Hemophilia B
|
0.090 |
GeneticVariation
|
disease |
BEFREE |
In conclusion, the present study demonstrated that the exogenous gene hFIX was effectively expressed following site‑specific targeting into the AAVS1 locus in MSCs; therefore, MSCs may be used as potential cell carriers for gene therapy of hemophilia B.
|
28112377 |
2017 |
|
Hemophilia B
|
0.090 |
Biomarker
|
disease |
BEFREE |
In this article we review the current state of AAV mediated gene therapy for hemophilia B in the clinic, detail progress since the first successful trial, and discuss alternative approaches from the AAV gene therapy field.
|
26524468 |
2016 |
|
Hemophilia B
|
0.090 |
Biomarker
|
disease |
BEFREE |
Vector capsid dose-dependent inflammation of transduced liver has limited the ability of adeno-associated virus (AAV) factor IX (FIX) gene therapy vectors to reliably convert severe to mild hemophilia B in human clinical trials.
|
25419787 |
2015 |
|
Hemophilia B
|
0.090 |
GeneticVariation
|
disease |
BEFREE |
Role of the vector genome and underlying factor IX mutation in immune responses to AAV gene therapy for hemophilia B.
|
24460861 |
2014 |
|
Hemophilia B
|
0.090 |
Biomarker
|
disease |
BEFREE |
Safety of AAV factor IX peripheral transvenular gene delivery to muscle in hemophilia B dogs.
|
20424599 |
2010 |
|
Hemophilia B
|
0.090 |
Biomarker
|
disease |
BEFREE |
These impressive results prompted initiation of two Phase I/II clinical trials to evaluate the safety of AAV-factor IX gene transfer to muscle and liver of patients with severe hemophilia B. Herein, we have reviewed results from studies in animals with hemophilia, early experience with the vector system in the clinic, recent innovative approaches in vector design and delivery, and strategies to circumvent immunological limitations.
|
15975012 |
2005 |
|
Hemophilia B
|
0.090 |
Biomarker
|
disease |
BEFREE |
In a staged approach, AAV-factor IX (AAV-F.IX) was first administered at doses of up to 1.8 x 10(12) vector genomes/kg (vg/kg) into the skeletal muscles of men with hemophilia B.
|
12463593 |
2002 |
|
Hemophilia A
|
0.060 |
GeneticVariation
|
disease |
BEFREE |
Thus, AAV gene therapies are likely to alter the treatment paradigm for hemophilia A and B.
|
31808868 |
2019 |
|
Hemophilia A
|
0.060 |
GeneticVariation
|
disease |
BEFREE |
Despite the initial success of liver-directed adeno-associated virus (AAV) gene therapy for hemophilia in clinical trials, long-term sustained therapeutic effects have yet to be seen.
|
30975639 |
2019 |
|
Cystic Fibrosis
|
0.060 |
Biomarker
|
disease |
BEFREE |
Areas covered: Herein, the authors focus on AAV gene therapy for CF, evaluating past experience with this approach and identifying ways forward, based on the progress that has already been made in identifying and overcoming the limitations of AAV gene therapy.
|
28657358 |
2017 |
|
Cystic Fibrosis
|
0.060 |
Biomarker
|
disease |
BEFREE |
All these studies showed that AAV gene therapy for CF is safe, but clinical benefit was not clearly demonstrated.
|
28726496 |
2017 |
|
Hemophilia A
|
0.060 |
Biomarker
|
disease |
BEFREE |
Here, we provide an overview of the clinical development of AAV gene transfer for hemophilia, as well as an outlook on future directions.
|
28411016 |
2017 |
|
Hemophilia A
|
0.060 |
Biomarker
|
disease |
BEFREE |
Adeno-associated virus (AAV) gene therapy vectors have shown the best outcomes in human clinical studies for the treatment of genetic diseases such as hemophilia.
|
28460646 |
2017 |
|
Cystic Fibrosis
|
0.060 |
GeneticVariation
|
disease |
BEFREE |
We investigated whether CF sputum acts as a barrier to leading adeno-associated virus (AAV) gene vectors, including AAV2, the only serotype tested in CF clinical trials, and AAV1, a leading candidate for future trials.
|
24869933 |
2014 |
|
Hemophilia A
|
0.060 |
Biomarker
|
disease |
BEFREE |
Adeno-associated viral (AAV) gene transfer of coagulation factor IX to skeletal muscle and liver of murine and canine models of hemophilia has resulted in sustained systemic expression and, in several studies, in complete cure of the bleeding disorder.
|
17266422 |
2007 |
|
Hemophilia A
|
0.060 |
Biomarker
|
disease |
BEFREE |
Adeno-associated viral (AAV) gene transfer of coagulation factor VIII and IX to skeletal muscle and liver of murine and canine models of hemophilia A and B have resulted in sustained systemic expression and, in several studies, in complete cure of the bleeding disorder.
|
15975012 |
2005 |
|
Cystic Fibrosis
|
0.060 |
Biomarker
|
disease |
BEFREE |
A study was conducted to assess health care worker exposure to tgAAVCF during the aerosolized administration of this experimental gene transfer agent in clinical trials for the treatment of cystic fibrosis (CF). tgAAVCF is a recombinant adeno-associated virus (AAV) genetically engineered to contain the human CF transmembrane conductance regulator cDNA.
|
15507460 |
2004 |
|
Cystic Fibrosis
|
0.060 |
GeneticVariation
|
disease |
BEFREE |
A prospective, randomized, double-blind, placebo-controlled, within-subjects, phase II clinical trial of the effect AAV-CFTR on clinical recurrence of sinusitis will determine the clinical efficacy of AAV gene therapy for CF.
|
10890777 |
1999 |
|
Cystic Fibrosis
|
0.060 |
AlteredExpression
|
disease |
BEFREE |
These studies provide novel insights into AAV gene expression, and this newly described promoter allows for the production of AAV vectors expressing CFTR in those differentiated cells affected in CF.
|
7679117 |
1993 |
|
Neoplasms
|
0.040 |
GeneticVariation
|
group |
BEFREE |
To circumvent this, here we employ adeno-associated virus (AAV) gene therapy vectors to express 3TSR alone or in combination with the CD47-binding peptide of TSP-1 and evaluate the impact on tumor development and survival in a mouse model of EOC.
|
31160686 |
2019 |
|
Neoplasms
|
0.040 |
AlteredExpression
|
group |
BEFREE |
To circumvent this, we developed a method to modify neurons with the genetic sequence for therapeutic monoclonal antibodies using adeno-associated virus (AAV) gene transfer vectors, directing persistent, local expression in the tumor milieu.
|
25501993 |
2015 |
|
Neoplasms
|
0.040 |
GeneticVariation
|
group |
BEFREE |
The therapeutic potential of adeno-associated viral (AAV) gene delivery of angiostatin in modulating tumor growth in vivo was evaluated.
|
14741778 |
2004 |
|
Neoplasms
|
0.040 |
Biomarker
|
group |
BEFREE |
The latter is of particular interest because the AAV integration site (AAVS1) is located on the long arm of chromosome 19 and 30-40% of human glioblastoma tumors are reported to have loss of heterozygosity in this region of chromosome 19q.
|
12542846 |
2002 |