Gene viral vector

Potentials for gene therapy, antisense oligonucleotides, genes, viral vectors, ex vivo therapy, ethical issues 71. 72, 76... 

Viral vectors Gene transfer Gene therapy... 

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)... 

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. 

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... 

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). 

The sindbis virus is simple, robust, capable of infecting non-dividing cells and generally supports high levels of gene expression. However, it does display a broad host range and, hence, lacks the inherent targeting specificity characteristic of an idealized viral vector. 

No matter what their composition, such synthetic gene delivery systems also meet various biological barriers to efficient cellular gene delivery. Viral vector-based systems are far less prone to such problems, as the viral carrier has evolved in nature to overcome such obstacles. Obstacles relate to ... 

Schatzlein, A. 2001. Non-viral vectors in cancer gene therapy principles and progress. Anti-Cancer Drugs 12(4), 275-304. 

Wu, N. and Ataai, M. 2000. Production of viral vectors for gene therapy applications. Current Opinion in Biotechnology 11(2), 205-208. 

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. 

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