Target Tissue of Choice For Gene Delivery System, Therapeutic, Raegeted, Retrovirus, Adenovirus, Bone narrow, Hematopoietic system, Transplantation

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Gene Theraphy
Gene Theraphy Introduction
Human Diseases Targeted for Gene Therapy
Some Human Diseases Targeted for gene therapy
Vectors and Other Delivery Systems for Gene therapy
Viruses as vectors
Retrovirus (RV) as a vector
Adenovirus (AV) as a vector
Adeno associated virus (AAV) as a vector
Lentiviruses as a vector
Non-viral DNA delivery systems
Synthetic particles as vectors
Transient Expression for gene therapy
Splicesome mediated trans-RNA splicing (SMART)
Ex Vivo vs In Vivo Gene Therapy
Target Tissue of Choice for Gen-Delivery System

	Target Tissue of Choice for Gen-Delivery System Both in ex vivo and in vivo approaches, there wilI be a target tissue in the body, where either the cells transfected in culture, will be transferred, or the vector carrying the therapeutic gene will be targeted, either for integration in the DNA of target cells (retrovirus) or for transient expression (adenovirus). Following are some of the target tissues. Bone marrow Bone marrow is a hematopoietic system, which is a suitable target for gene therapy, since well developed procedures for bone-marrow transplantation are available. The pluripotent hematopoietic stem cells (HSC) constitute .01 to 0.1 % of human bone marrow cells which are therefore, considered as an ideal target tissue. Gene transfer to HSC is also considered to be the best example of ex vivo gene therapy, and transduction of even few HSCs is sufficient to give enough transduced cells by multiplication.
Muscle Muscles consist of myoblasts, which are used as target cells, if muscles are the target tissues for gene therapy. Myoblasts infected with retrovirus carrying a therapeutic gene, when injected. exhibited sustained expression of gene for atleast six months in animal models. The risk, however, is that myoblasts may migrate to other tissues and express there in the absence of tissue specific expression. Adenovirus vector containing a reporter gene has shown efficient transduction of muscle after direct injection in mouse. Myoblasts are also suitable for direct gene transfer using in vivo approach Stable gene expression of injected DNA (present as episomes) was achieved in cardiac and skeletal muscles of mouse, although the efficiency was low in primates, when ‘gene gun' was tried.
Liver Liver contains hepatocytes, which can be used as target cells, using both ex vivo and in vivo approaches. However, they can not be extensively manipulated in culture, because they Undergo few cell divisions. Further, the transduction efficiencies with retroviral vectors are rather low. Nevertheless, retrovirus-mediated ex vivo transfer of disease related human genes has been successfully achieved Hepatocytes, which are generally non-dividing cells, can be activated into cell division by hepatactomy, so that retrovirus mediated in vivo gene transfer can be achieved. Adenovirus, adeno-associated virus and some non-viral vectors have also been used for in vivo targeting of DNA to the liver.
Other tissues (brain, trachea) Cells like brain cells or neurons (neurological disorders) and those belonging to tracheal epithelium or lung (e.g. 'cystic fibrosis' diseases) are difficult targets, because cells can not be easily harvested for ex vivo approach and the tissues are generally inaccessible for in vivo approach. However, HSV -1 vectors have been used to transduce neurons both ex vivo and in vivo. Similarly adenovirus mediated and liposome mediated gene delivery to respiratory epithelium has been achieved in some animal models (e.g. rat). Cell types including keratinocytes, fibroblasts, myoblasts, vascular endothelial cells/smooth muscle cells are also used for delivering genes whose products are secreted into the circulating blood. In vivo gene transfer into a specific blood vessel and lymphocytes has also been achieved