Vectors viral

Viral vectors Gene transfer Gene therapy... 

Viral vectors are usually classified by the characteristics of the parental viius. Based on the viral genome, one can distinguish between DNA and RNA viruses (for details see [1, 2]). 

Presently, 1,260 gene-therapy trials are underway worldwide (Tables 1 and 2). For details see http // www.wiley.co.uk/genetherapy/clinical/. Almost three fourths of all trials are based on viral vectors. The vast majority of nonviral gene-therapy trials use naked/ plasmid DNA (18% of all gene-therapy trials). 

An important safety issue of viral vectors is whether or not the recombinant viruses are able to replicate in the infected cells. Replication of viral vectors is unwanted in most gene-therapy approaches. Therefore, replication-defective vectors have been designed, which are able to perform only one initial infectious cycle within the target cell. In addition, replication-competent vectors have been designed, which are able to productively infect the target cell and to spread in the target tissue. 

Gene-therapy Vectors. Table 2 List of most common therapeutic genes used in gene-therapy trials (viral and non viral vectors)... 

VIPomas Viral Proteases Viral Vectors Virostatics Vitus-like Particle Vitamin A Vitamin B1 Vitamin B2 Vitamin B6 Vitamin B12 Vitamin C Vitamin D... 

The nasal tissue is highly vascularized and provides efficient systemic absorption. Compared with oral or subcutaneous administration, nasal administration enhances bioavailability and improves safety and efficacy. Chitosan enhances the absorption of proteins and peptide drugs across nasal and intestinal epithelia. Gogev et al. demonstrated that the soluble formulation of glycol chitosan has potential usefulness as an intranasal adjuvant for recombinant viral vector vaccines in cattle [276]. 

Viruses are infectious particles formed by nucleic acid, proteins, and in some cases lipids. As viruses (for example, retro- and adenoviruses) transfer viral genes into cells with high efficiency, modified forms are sometimes used as vectors for gene transfer. However, procedures using virus-based vectors are often significantly more complicated and time-consuming than other transfection methods. In addition, viral vectors are potentially hazardous, and biological safety issues need to be considered carefully. Therefore, techniques that combine... 

HIV phenotype A type of resistance testing for human immunodeficiency virus (HIV) in which a patient s blood sample is obtained, and the patient s HIV genes that encode for reverse transcriptase and protease are removed and placed in an HIV viral vector. This viral vector is replicated in a cell culture system with varying concentrations of antiretrovirals. A drug concentration-viral inhibition curve is developed and the concentration needed to inhibit 50% of the patient s virus is reported. This is used to predict resistance versus susceptibility. 

Most of the viral vectors were constructed using (1) the Autographa californica nuclear polyhedrosis virus (AcNPV), which is able to infect moth species, Spodoptera frugiperda ovarian cell lines and, in specific conditions, Drosophila cells (2) the Bombyx mori nuclear polyhedrosis virus (BmNPV), which is able to infect silkworm cells. To broaden the range of infection of hosts, a hybrid virus was generated [118,119]. 

The technology platform is categorized within three areas Viral vector technologies (for gene expression), Biomanufacturing resources (for protein production) and Molecular improvement and medical discovery technologies (for discovery of biomolecules, genes and proteins, and the improvements of their functionality). 

Fig. 1.11 Applications of LDHs as (A) non-viral vector in gene therapy for transfection of DNA to the cell nucleus, and (B) as matrix for enzymes immobilization in the development of biosensors.

Roy, I., Ohulchanskyy, T.Y., Bharali, D.J., Pudavar, H.E., Mistretta, R.A., Kaur, N. and Prasad, P.N. (2005) Organically modified silica nanoparticles A non-viral vector for in-vivo gene delivery and expression. Proceedings of the National Academy of Sciences of the United States of America, 102, 11539-11544. 

Miller, A.D., The problem with cationic liposome/micelle-based non-viral vector systems for gene therapy, Current Medicinal Chemistry, 2003, 10, 1195-1211. 

Boeckle S, Wagner E (2006) Optimizing targeted gene delivery chemical modification of viral vectors and synthesis of artificial virus vector systems. AAPS J 8 E731-E742... 

Wagner E (2008) Converging paths of viral and non-viral vector engineering. Mol Ther 16 1-2... 

Compared with whole plants, there has been limited development of foreign protein expression systems specifically for use in tissue culture. Some modifications of expression constructs have resulted in improved protein accumulation or have allowed simplified protein recovery. However, in general, modified expression systems have been tested only in a restricted number of cases and have not resulted in the large increases in product yield required for plant cultures to compete with other foreign protein production vehicles. Transient expression techniques, for example using viral vectors, that have been developed for use in whole plants have not yet been applied in plant tissue culture. 

Further improvements to vims expression systems include trans-complementation of some of the virus functions from transgenic host plants (P12 plants for AlMV). By integrating parts of the viral vector into the plant chromosome, this system has the potential for multiple technical solutions that could overcome limitations of classical viral vectors [33]. Viral vectors can be used as molecular switches for tightly controlled, high-level transgene expression (Hull et al. unpublished data). 

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