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Vectors and Other Delivery Systems for Gene Therapy
Gene delivery for gene therapy, is achieved by one of the following two methods (i) viral transduction, involving introduction of a modified virus carrying foreign gene and (ii) physical transfection involving the use of either 'chemical methods' like calcium phosphate, liposomes and molecular conjugates or 'physical methods' like electro­poration and particle acceleration (biolistics). Since transduction gives stable integration and autonomous replication. vector mediated gene transfer is preferred and a variety of vectors have been tried.

TComparison of gene delivery systems for gene therapy

Deliving system

Integration

Transduction

Comments

I. Viral vectors

+

-

Low titre

2. Adenovirus  (AV)

+

-

 

3. Adeno-associated

+

-

Helper virus

4. Lentiviruses (Herpes simplex virus)

+

?

pathogenic

II. Physical methods

 

 

 

1. Receptor mediated

+

+

Enhanced by

2. Direct injection

-

+

Muscle

3. Lipofection

+

+

Gene gum



However, one of the serious problems is the nonavailability of an ideal vector, which must achieve regulated and sustained expression of foreign genes in specific cells or tissues. This requires that a foreign gene be included in a gene construct, which either replicates autonomously or gets integrated with an active region of the genome of the host. Furthermore, the whole process must be safe, efficient and selective. Among the available vectors, each vector satisfies some of these features but none fulfils all the requirements.

Characteristics of different types of vectors used for delivery of genes

Retrovirus

Adenovirus

Other Viral vectors

Non viral vectors

RNA genome  (e.g. MMLV)

Linear double stranded DNA genome

DNA (adeno-associated virus or AAV, HSV1)

DNA protein complex

Reverse transcribed

Does not integrate  in host genome

It integrates

DNA entrapped in endosomes

Viral genome integration in host genome; is not lost

Human kidney cell line supplying EIA products Dividing cells not necessary

 

Cultured hepatocytes

Suitable host : proliferating Tissue

EIA region of virus, needed for gene expression and replication, is deleted and replication by therapeutic gene

 

 

Therapeutic gene is inserted in viral genome

Can infect non dividing cells (major advantage)