Gene delivery viral vectors

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 ... 

Genes can be introduced by the application of naked DNA alone however, better efficiency is achieved when the DNA is incorporated into a delivery vector. These delivery vectors consist of viral, those utilizing modified virus particles for DNA delivery, and nonviral, for which various chemicals are used to aid DNA packaging and delivery. Viral vectors confer significantly better transfection efficiency than nonviral vectors however, recently the toxicity and oncogenic side effects of viral vectors have become a major concern (6). Nonviral vectors do not have such serious side effects but lack the efficiency (7). 

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. 

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... 

Some 24 per cent of all gene therapy clinical trials undertaken to date have employed retroviral vectors as gene delivery systems. Retroviruses are enveloped viruses. Their genome consists of ssRNA of approximately 5-8 kb. Upon entry into sensitive cells, the viral RNA is reverse transcribed and eventually yields double-stranded DNA. This subsequently integrates into the host cell genome (Box 14.1). The basic retroviral genome contains a minimum of three structural genes ... 

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. 

Kataoka, K., Harashima, H., Gene delivery systems Viral vs. non-viral vectors. Adv Drug Deliv Rev 52, 151 (2001). 

Theoretically, this appears to be a htting solution to gene problems. However, there are problems, such as immune and inflammation responses, toxicity, and means to target the intended cells. Non viral vectors may overcome the problems with viral delivery agents. Lipids, in the form of liposomes and other lipid complexes, are being studied. Injection of DNA directly into a patient s muscle cells is another avenue being researched. 

Figure 2.6. Strategies for drug delivery across the blood-brain barrier (BBB). The physical, pharmacological and physiological approaches are discussed in the text. Present experimental attempts at viral gene delivery would also be classified as invasive because of the intracerebral administration of the vector.

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