Challenges and strategies: The immune responses in gene therapy
@article{Zhou2004ChallengesAS, title={Challenges and strategies: The immune responses in gene therapy}, author={Hai-sheng Zhou and De-Pei Liu and Chih-Chuan Liang}, journal={Medicinal Research Reviews}, year={2004}, volume={24} }
The host immune responses, including T lymphocytes mediated immune response and humoral immune responses are the important parts of the challenges in gene therapy. There are some potential immunostimulants in gene delivery systems, such as viral and non‐viral vectors. Viral gene products, transgene products, viral proteins derived from viral particles required by dead‐end infection, and CpG DNA in plasmid may play important roles in inducing the host immune responses when foreign genes are…
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References
SHOWING 1-10 OF 88 REFERENCES
Improvements in gene therapy: averting the immune response to adenoviral vectors.
- BiologyBioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy
- 2002
Despite considerable progress over the past decade in the generation of gene transfer systems with reduced immunogenic properties, the remaining immunogenicity of many gene therapy vectors is still the major hurdle, preventing their frequent application in clinical trials.
Designing gene therapy vectors: avoiding immune responses by using tissue-specific promoters
- BiologyGene Therapy
- 2001
It is shown thatHBsAg-specific humoral or cell-mediated responses are not induced in mice when the muscle-specific human muscle creatine kinase promoter is used in place of the ubiquitous cytomegaloviral promoter to drive expression of HBsAg.
Induction of immune tolerance to coagulation factor IX antigen by in vivo hepatic gene transfer.
- BiologyThe Journal of clinical investigation
- 2003
Induction of immune tolerance to a secreted human coagulation factor IX (hF.IX) antigen by adeno-associated viral gene transfer to the liver is demonstrated, supporting the relevance of these data for treatment of hemophilia B and other genetic diseases.
Immune responses to viral antigens versus transgene product in the elimination of recombinant adenovirus-infected hepatocytes in vivo.
- Biology, MedicineGene therapy
- 1996
It is confirmed that B cell-mediated events do not participate in destruction of hepatocytes in vivo, despite the production of virus- and beta-gal-specific antibodies, which confirm the hypothesis that viral gene expression elicits host responses that contribute to the problem of transgene instability.
Molecular basis of the inflammatory response to adenovirus vectors
- BiologyGene Therapy
- 2003
An understanding of the innate response to adenovirus vectors is essential to overcome the last remaining hurdle to improve the safety and effectiveness of these agents.
Cellular immune response to adenoviral vector infected cells does not require de novo viral gene expression: implications for gene therapy.
- Biology, MedicineProceedings of the National Academy of Sciences of the United States of America
- 1998
It is proposed that cells infected with RDAd vectors present antigens for recognition by class 1 major histocompatibility complex-restricted cytotoxic T lymphocytes by a mechanism that does not require viral replication or de novo protein synthesis.
Promoter Attenuation in Gene Therapy: Interferon-γ and Tumor Necrosis Factor-α Inhibit Transgene Expression
- Biology
- 1997
The data indicate that the cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) inhibit transgene expression from certain widely used viral promoters/enhancers delivered by adenoviral, retroviral or plasmid vectors in vitro.
Effect of immune response on gene transfer to the lung via systemic administration of cationic lipidic vectors.
- Biology, MedicineAmerican journal of physiology. Lung cellular and molecular physiology
- 1999
It is reported that cationic lipid-protamine-DNA complexes, but not each component alone, can induce a high level of cytokine production, including interferon-γ and tumor necrosis factor-α, and it is demonstrated that LPD administration triggers apoptosis in the lung, a phenomenon that may be mediated in part by the two cytokines.
Promoter attenuation in gene therapy: interferon-gamma and tumor necrosis factor-alpha inhibit transgene expression.
- BiologyHuman gene therapy
- 1997
Standard gene therapy vectors in current use may be improved by altering cytokine-responsive regulatory elements by determining the mechanisms involved in cytokines-regulated vector gene expression to improve the understanding of the cellular disposition of vectors for gene transfer and gene therapy.
Induction of immunity to antigens expressed by recombinant adeno-associated virus depends on the route of administration.
- BiologyClinical immunology
- 1999
A possible role for rAAV in the immunotherapy of malignancies and viral infections is suggested, although induced antibody responses to AAV may limit its ability to be administered for repeated vaccinations.