Adeno associated virus

Nonintegrating Vectors Derived from Adenovirus, Adeno-Associated Virus,... 

The small adeno-associated virus (AAV) vectors can be easily prodnced, have not been found to canse major toxicity, and persist in the transduced hepatocyte typically as an episomal transcriptionally active DNA molecule. Because of the limited packaging capacity for foreign DNA of 4.6 kb, these vectors have been preferentially nsed to express small transgenes and shRNAs directed against HBV or HCV... 

Adeno-associated virus Direct injection of naked DNA... 

Figure 14.2 Vectors used thus far in gene therapy trials. Others are mainly viral-based and include the use of pox, vaccinia and adeno-associated viruses, as well as herpes simplex virus. Data adapted from www.wiley. co.uk/genemed/clinical...

A number of additional viral types may also prove useful as vectors in the practice of gene therapy. Chief amongst these are the adenoviruses. Adeno-associated virus, the herpes virus, and a number of other viruses, are also being considered (Table 14.2). 

Additional viruses that may prove of some use as future viral vectors include adeno-associated virus and herpes virus. Adeno-associated virus is a very small, single-stranded DNA virus its genome consists of only two genes. It does not have the ability to replicate autonomously and can do so only in the presence of a co-infecting adenovirus (or other selected viruses). 

Gene Therapies. The types of vectors that have been used or proposed for gene transduction include retrovirus, adenovirus, adeno-associated viruses, other viruses (e.g., herpes, vaccinia, etc.), and plasmid DNA. Methods for gene introduction include ex vivo replacement, drug delivery, marker studies, and others and in vivo, viral vectors, plasmid vectors, and vector producer cells. 

Viral Vectors. The direct administration of a viral vector (e.g., retrovirus, adenovirus, adeno-associated virus, herpes, vaccinia) to patients. 

Duan, D., Z. Yan, Y. Yue, W. Ding, and J. F. Engelhardt. 2001. Enhancement of muscle gene delivery with pseudotyped adeno-associated virus type 5 correlates with myoblast differentiation. J Virol 75(16) 7662—71. 

Retrovirus Adenovirus Adeno- Associated Virus Liposomes Naked DNA... 

For loss-of-fundion mutations gene replacement therapy usng retroviruses, adenoviruses, adeno-associated viruses, or liposomes as vectors... 

Costello, E., Saudan, P., Winocour, E., Pizer, L., and Beard, P. (1997) High mobility group chromosomal protein 1 binds to the adeno-associated virus replication protein (Rep) and promotes... 

Two types of DNA viruses have also been used in human gene therapy trials. Adenoviruses, double-stranded DNA viruses, can efficiently carry a larger gene into cells even if they are not dividing, but the genetic information does not become inserted into the cell s genetic material and the information may rapidly be lost. Adeno-associated virus vectors, made from small single-stranded... 

D) Adeno-associated virus (AAV) vector delivered to skeletal muscle... 

Manning, W.C., X. Paliard, S. Zhou, M. Pat Bland, A.Y. Lee, K. Hong, C.M. Walker, J.A. Escobedo, and V. Dwarki, Genetic immunization with adeno-associated virus vectors expressing herpes simplex virus type 2 glycoproteins B and D. J Virol, 1997. 71(10) 7960-2. 

BOX 15.2. ENGINEERING OF ADENO-ASSOCIATED VIRUS AS A GENE THERAPY FOR HEMOPHILIA... 

Recently another novel method has been described for factor VIII gene transfer in patients with hemophilia A that avoids the use of viral vectors. The transfer was safe and well tolerated, and provided a modicum of benefit [8], Up until now the most promising strategy for factor VIII gene transfer had relied on adeno-associated virus (AAV). 

Adeno-associated virus is the most innocuous of viral vectors. It is nonpathogenic and its genome can be engineered to only encode for the therapeutic gene. There... 

Clinical Applications of Adeno-Associated Virus. There have been many preclinical demonstrations of successful production of therapeutic proteins by engineered AAV [37-39]. The major clini-... 

Qing, K., C. Mah, I Hansen, S. Zhou, V. Dwarki, and A. Srivastava, Human fibroblast growth factor receptor 1 is a co-receptor for infection by adeno-associated virus 2. Nat Med, 1999. 5(1) 71-7. 

Summerford, C., IS. Bartlett, and R.J. Samulski, AlphaVbetaS integrin a coreceptor for adeno-associated virus type 2 infection. Nat Med, 1999. 5(1) 78-82. 

Summerford, C., and R.I Samnlski, Membrane-associated heparan sulfate proteoglycan is a receptor for adeno-associated virus type 2 virions. J Virol, 1998. 72(2) 1438-45. 

Wu, P, W. Xiao, T. Conlon, I Hnghes, M. Agbandje-McKenna, T. Ferkol, T. Flotte, and N. Muzyczka, Mutational analysis of the adeno-associated virus type 2 (AAV2) capsid gene and construction of AAV2 vectors with altered tropism. J Virol, 2000. 74(18) 8635 7. 

Ried, M.U., A. Girod, K. Leike, H. Buning, and M. Hallek, Adeno-associated virus capsids displaying immunoglobulin-binding domains permit antibody-mediated vector retargeting to specific cell surface receptors. J Virol, 2002. 76(9) 4559-66. 

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