Viral vectors herpes simplex virus

Herpes-viral vector Herpes simplex virus No... 

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...

There is a wide variety of vectors used to deliver DNA or oligonucleotides into mammalian cells, either in vitro or in vivo. The most common vector systems are based on viral [retroviruses (9, 10), adeno-associated virus (AAV) (11), adenovirus (12, 13), herpes simplex virus (HSV) (14)] andnonviral [cationic liposomes (15,16), polymers and receptor-mediated polylysine-DNA] complexes (17). Other viral vectors that are currently under development are based on lentiviruses (18), human cytomegalovirus (CMV) (19), Epstein-Barr virus (EBV) (20), poxviruses (21), negative-strand RNA viruses (influenza virus), alphaviruses and herpesvirus saimiri (22). Also a hybrid adenoviral/retroviral vector has successfully been used for in vivo gene transduction (23). A simplified schematic representation of basic human gene therapy methods is described in Figure 13.1. 

Approximately 90% of the population is infected with herpes simplex virus type 1 (HSV-1), and at least 10% with HSV-2 (Nahmias and Roizman, 1973 Whidey, 1997). Humans are the only natural reservoir for this infecdon, and no vectors are involved in d ansmission of this virus (Stanberry et al., 2004). HSV-1 primary infecdon occurs mainly in childhood, and HSV-2 infecdon occurs predominantly in sexually acdve adolescents and young adults. Aerosols or close contact are the primary mechanisms of viral d ansmission. Although dansmitted by different routes and involving different parts of the body, these two viral subtypes have similar epidemiology and clinical manifestadon. 

Frenkel N, Spaete RR, Vlazny DA, Deiss LP, Locker H (1982) The herpes simplex virus amplicon—a novel animal-virus cloning vector. hr Eucaryodc Viral Vectors (Gluzman Y, ed), pp 205—209. New York Cold Spring Harbor Laboratory. 

The most frequently used viral vectors in clinical trials so far are retroviruses and adenoviruses (Table 7.1-1). Several other viral vectors are in preclinical development or are under clinical evaluation, including adeno-associated virus (AAV), lentivirus, herpes simplex virus (HSV), and others. 

Viruses have evolved to achieve robust gene expression within a host s cell. For this reason, viral gene deUvery represents a substantial amount of current gene therapy research, and so far, the best way to deliver a gene to a desired cell type. Viral vector delivery to brain tumors has been investigated using different types of viruses, including adenovirus (Ad), herpes simplex virus (HSV), retrovirus (RV), measles virus, adeno-assodated virus (AAV), Newcastle disease virus (NDV), Semliki Forest virus, vaccinia virus, and reovirus [110]. The most commonly used viruses represented in experimental brain tumor therapies are the HSV and Ad viruses. 

However, a reporter gene needs to be introduced into the cells to be imaged. Viral gene vectors (retrovirus, adenovirus, Herpes simplex virus, etc.) have a high transfection efficiency, but may lead to immunogenic response, whereas nonviral systems (naked DNA, liposomes, etc.) are less immunogenic and easier to manufacture, but lead to a less efficient transfection (3). 

Other viral vectors have also been developed for use in gene therapy. These include the herpes simplex virus, the vaccinia virus and Sinbis virus. However, these vectors have not been widely studied and it is not clear what advantages they may hold over retroviral, adenoviral or AAV vectors. Recently, limited-replicating viral vectors, such as the Onyx-015 virus, have been developed. The Onyx virus is an ElB deleted adenovirus that can only replicate in p53 deficient cells advantage ofthese vectors is that their replication is limited mainly to tumour cells and that permitting the replication of the virus produces more efficient transfection of the tumour cells. Studies are ongoing to demonstrate the usefulness and safety of replicating vectors. 

Other viral vectors refers to recombinant canarypox vims, vaccinia virus, fowlpox, and herpes simplex vims. Other nonviral vector refers to RNA transfer and antisense delivery. 

Despite improvement in nonviral gene delivery systems, viral vectors continue to have higher efficiency in most experimental systems. Adenovirus, adeno-associated virus, retrovirus, lentivirus, herpes simplex viras, and others have been used both in the laboratory, and to a much lesser extent, in human trials. Of these potential vectors, studies of adenoviras in the pulmonary circulation are the only ones in the published literature. 

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