Chemical Methods to Enhance Delivery and Disadvantages of Gene Therapy

Chemical Methods to Enhance Delivery 

Oligonucleotides

In the disease process, for the inactivation of the genes in gene therapy; the use of synthetic oligonucleotides is involved. This is achieved by so many different methods. One strategy uses small RNA molecules called SiRNA to signal the cell to cleave specific unique sequences in the mRNA transcript of the faulty gene. This results in the disruption of translation of the faulty mRNA and consequently expression of the gene. . To disrupt the transcription of the faulty gene, another strategy uses antisense specific to the targeted gene.

Lipoplexes and polyplexes

For the improved delivery of the new DNA into cell, DNA must be secured from positively charged and damage. Primarily, neutral lipids and anionic were used for the construction of lipoplexes for synthetic vectors.

Dendrimers

Dendrimer is spherical shaped, highly branched macromolecule. The particle surface may be functionalized in so many ways and so many properties of the resulting construct are determined by its surface. In actual it is promising to construct a cationic dendrimer, i.e. one with a + surface charge.

When in the presence of RNA or DNA (genetic material), charge complimentarity leads towards a temporary association of nucleic acid with cationic dendrimer. On reaching its end destination, via endocytosis the dendrimer-nucleic acid complex is then taken into cell. 

Hybrid methods

There have been some hybrid methods that are developed that combines two or more than two techniques.(Woods N.B.,et al, 2006).

One example is Vitrosomes; they combine an inactivated influenza or HIV virus with liposomes. In respiratory epithelial cells, this has been shown to have more efficient gene transfer than either liposomal or viral methods alone. Other methods include mixing of other vectors with hybridising viruses or cationic lipids.(Hongjie et al, 2005)

Disadvantages of Gene Therapy

Without some associated risk, no therapy is established or experimented. There are still so many risks associated with the human gene therapy because it is a relatively new procedure. All of the risks are still not understandable by the scientists. There has not been enough time to complete the details about this study and recognize how gene therapy works and the entire problem it possess. In the field of gene therapy, surely the safety considerations remained important.(Baun C et al, 2003).Some problem of Gene therapy includes:  

Short-lived nature of gene therapy: For any condition, before the gene therapy becomes a permanent cure, the introduction of therapeutic DNA into targeted cells must remain functional the cells containing therapeutic DNA must be stable and long-lived. The rapidly dividing nature of many cells prevents gene therapy from achieving any long term benefits. The patients of gene therapy will have to undergo multiple rounds if the desire response is not gained. Furthermore, the new incorporated genes may fail to express it or the virus does not produce the desired response.  

• Immune response: The immune system has evolved to attack the invader anytime a foreign object is introduced into human tissues. There is always a possibility of the risk of encouraging the immune system in a way that reduces the effectiveness of gene therapy. Moreover, immune system’s improved response to invaders makes it tough for gene therapy in patients to repeat.  (Rochat T et al, 2002)

• Problem with viral vectors: Viruses that are mostly the carrier choice in gene therapy studies shows a variety of problems to the patients; immune inflammatory response, toxicity, targeting issues and gene control issues. Furthermore, once inside the patient there is always the fear that viral vector may recover the ability to cause death.

• Multigenic disorders: For gene therapy, disorders or conditions that arise from mutations in a single gene are the best candidates. Unluckily, some commonly occurring disorders are combined effects of variations in many genes. These common disorders are heart disease, Alzheimer’s disease, high blood pressure, diabetes and arthritis. Multifactorial or multigenic disorders would be difficult to treat efficiently using the gene therapy. (Walther W and Stein U., 2000).

• Insertional mutagenesis: The chief problem that is encountered by the geneticists is that if the DNA is integrated in the wrong place in the genome, the virus may target the wrong cells (Durai S et al, 2005) For instance, In clinical trial it has occurred in X-SCID (X linked severe combined immunodeficiency) patients, in which by using a retrovirus hematopoietic stem cells were transduced with a corrective transgene. This leads towards the developments of T cell leukaemia in three out of 20 patients.