New non-Viral Vectors for Gene Therapy
The know how on amphiphilic aggregates such as micelles or liposomes allowed us to set up a program, in collaboration with other European groups, on the preparation of new lipidic vectors for complexing DNA for Gene Therapy. The program includes: a) the preparation of new cationic amphiphilic molecules to be used as components of liposomes formed by natural lipids; b) the morphological, physico chemical and biological characterization of the obtained liposomes and of their DNA complexes. The correlation of the physico-chemical and biological features should allow to design specific and efficient vectors. Preliminary results are quite encouraging.
Many diseases originate from a defect in the DNA. Some faulty genes, called oncogenes, provoke uncontrollable cell growth and cell division, culminating in cancer development. In other cases, a defective gene may give rise to a defective protein and/or to its rapid degradation. Additionally, the gene may not be transcribed at all. Historically, these disorders have been symptomatically treated, rather than curing their molecular cause. Somatic gene therapy is an alternative approach aimed at treating the causes of genetic disorders .
The aim of gene therapy is to provide specific cells of a patient with the genetic information necessary to produce therapeutic proteins for correction of diseases.
Practically it consists in inserting new genes into human cells. The goal is the expression of the previously missing or defective protein, of a therapeutic protein or (in cancer therapy) of a new protein that will destroy the cells either by the attivation of the immune system or by a drug. The first clinical studies began in 1990, since then, progress has been accomplished; however, from the gained experience it is clear that protocols developed until now have resulted in inadequate performances .
A major issue that has kept gene therapy from becoming an effective and general treatment for many diseases, concerns the nature of the vectors. In order for a therapeutic gene to reach the cells affected by the disorder, a specific vector has to be used for transporting the genetic material inside the cell in an efficient and harmless manner.
The ideal vector should be:
-target specificity
-absence of immunogenicity
-high transfection efficiency
Most protocols are based on viral vectors. Gene therapists have taken advantage of virus capacity of entering cells, replicating and propagating to neighbouring cells and have developed modified viral vectors carrying therapeutic genes able to efficiently and safely transduce cells. However, all viral vectors induce an immune response of the host.
Non viral vectors such as cationic polymers or lipids able to complex DNA give less efficient transfection in comparison to viral vectors, but are less immunogenic and easier to manufacture and have high versatility. This versatility can allow to overcome the low transfection efficiency and target specificity.
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