Alipogene tiparvovec: Difference between revisions
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Recombinant AAV (as for Glybera) is non-integrating. |
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==Mechanism== |
==Mechanism== |
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The [[adeno-associated virus]] serotype 1 (AAV1) viral vector delivers an intact copy of the human [[lipoprotein lipase]] (LPL) gene. AAV1 targets skeletal muscle cells, which are normally the main tissue for LPL protein production. Data from the clinical trials indicates that fat concentrations in blood were reduced between 3 and 12 weeks after injection, in nearly all patients. The advantages of AAV include apparent lack of pathogenicity, delivery to non-dividing cells and |
The [[adeno-associated virus]] serotype 1 (AAV1) viral vector delivers an intact copy of the human [[lipoprotein lipase]] (LPL) gene. AAV1 targets skeletal muscle cells, which are normally the main tissue for LPL protein production. Data from the clinical trials indicates that fat concentrations in blood were reduced between 3 and 12 weeks after injection, in nearly all patients. The advantages of AAV include apparent lack of pathogenicity, delivery to non-dividing cells, and non-integrating in contrast to [[retrovirus]]es, which show random insertion with accompanying risk of [[cancer]]. AAV also presents very low [[immunogenicity]], mainly restricted to generating neutralizing [[antibodies]], and little well defined [[Antibody-dependent cellular cytotoxicity|cytotoxic response]].<ref name="ChirmulePropert1999">{{cite journal |author=Chirmule N, Propert K, Magosin S, Qian Y, Qian R, Wilson J |title=Immune responses to adenovirus and adeno-associated virus in humans |journal=Gene Therapy |volume=6 |issue=9 |pages=1574–83 |year=1999 |month=September |pmid=10490767 |doi=10.1038/sj.gt.3300994}}</ref><ref name="HernandezWang1999">{{cite journal |author=Hernandez YJ, Wang J, Kearns WG, Loiler S, Poirier A, Flotte TR |title=Latent Adeno-Associated Virus Infection Elicits Humoral but Not Cell-Mediated Immune Responses in a Nonhuman Primate Model |journal=Journal of Virology |volume=73 |issue=10 |pages=8549–58 |date=1 October 1999|pmid=10482608 |pmc=112875 |url=http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=10482608 }}</ref><ref name="PonnazhaganMukherjee1997">{{cite journal |author=Ponnazhagan S, Mukherjee P, Yoder MC, ''et al.'' |title=Adeno-associated virus 2-mediated gene transfer in vivo: organ-tropism and expression of transduced sequences in mice |journal=Gene |volume=190 |issue=1 |pages=203–10 |year=1997 |month=April |pmid=9185868 |doi=10.1016/S0378-1119(96)00576-8}}</ref> The cloning capacity of the vector is limited to replacement of the virus's 4.8 kilobase genome. |
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==References== |
==References== |
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Revision as of 02:01, 9 March 2013
Glybera is a gene therapy treatment that compensates for lipoprotein lipase deficiency (LPLD), which can cause severe pancreatitis.[1] In July 2012, the European Medicines Agency recommended it for approval, the first recommendation for a gene therapy treatment in either Europe or the United States. The recommendation was endorsed by the European Commission in November 2012[2][3] and commercial rollout is expected in late 2013.[4]
Mechanism
The adeno-associated virus serotype 1 (AAV1) viral vector delivers an intact copy of the human lipoprotein lipase (LPL) gene. AAV1 targets skeletal muscle cells, which are normally the main tissue for LPL protein production. Data from the clinical trials indicates that fat concentrations in blood were reduced between 3 and 12 weeks after injection, in nearly all patients. The advantages of AAV include apparent lack of pathogenicity, delivery to non-dividing cells, and non-integrating in contrast to retroviruses, which show random insertion with accompanying risk of cancer. AAV also presents very low immunogenicity, mainly restricted to generating neutralizing antibodies, and little well defined cytotoxic response.[5][6][7] The cloning capacity of the vector is limited to replacement of the virus's 4.8 kilobase genome.
References
- ^ European Agency Backs Approval of a Gene Therapy July 20, 2012
- ^ Gallagher, James. (2012-11-02) BBC News – Gene therapy: Glybera approved by European Commission. Bbc.co.uk. Retrieved on 2012-12-15.
- ^ Richards, Sabrina. "Gene Therapy Arrives in Europe". The Scientist. Retrieved 16 November 2012.
- ^ Press Release. UniQure (2012-11-02). Retrieved on 2012-12-15.
- ^ Chirmule N, Propert K, Magosin S, Qian Y, Qian R, Wilson J (1999). "Immune responses to adenovirus and adeno-associated virus in humans". Gene Therapy. 6 (9): 1574–83. doi:10.1038/sj.gt.3300994. PMID 10490767.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Hernandez YJ, Wang J, Kearns WG, Loiler S, Poirier A, Flotte TR (1 October 1999). "Latent Adeno-Associated Virus Infection Elicits Humoral but Not Cell-Mediated Immune Responses in a Nonhuman Primate Model". Journal of Virology. 73 (10): 8549–58. PMC 112875. PMID 10482608.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Ponnazhagan S, Mukherjee P, Yoder MC; et al. (1997). "Adeno-associated virus 2-mediated gene transfer in vivo: organ-tropism and expression of transduced sequences in mice". Gene. 190 (1): 203–10. doi:10.1016/S0378-1119(96)00576-8. PMID 9185868.
{{cite journal}}: Explicit use of et al. in:|author=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link)