Erano gli anni ’70 quando French Anderson mandò al New England Journal of Medicine un articolo in cui anticipava la possibilità di guarire le malattie ereditarie inserendo nell’organismo i geni mancanti o sostituendo quelli difettosi. "Impubblicabile perchè di sola fantascienza" rispose la rivista. Nel 1990, Anderson e Michael Blease riuscirono nell’impossibile e conclusero con successo il primo intervento reale di terapia genica sulla bimba di 4 anni, Ashanti De Silva, destinata a morire di immunodeficienza perché priva the gene that produces the enzyme ADA. In the world today, hundreds of experimental interventions using gene therapy.
What are the problems, opportunities, hopes to use this frontier of medicine?
When we talk about gene therapy, we mean the transfer of genetic material in order to prevent or cure a disease. In practice, you try to transfer into cancer cells a genetic code "working" system, which replace the missing or defective gene. Candidates for this type of therapy are some hereditary diseases, in which there is one and the same genetic defect (monogenic), various infectious diseases is not curable with normali trattamenti antivirali (HIV) ed alcuni tipi di tumore, quali melanoma, leucemie, sarcomi e neoplasie del tessuto nervoso, gastrointestinali, uro-genitali e ginecologiche.
Per ottenere un risultato terapeutico efficace vanno superati vari ostacoli. In primis, abbiamo la necessità di conoscere il gene responsabile della malattia, clonarlo e quindi riprodurre in laboratorio la versione corretta e funzionante. Poi dobbiamo disporre di un vettore che ci permetta di inserire il DNA da noi prodotto all’interno della cellula malata. Questo vettore deve essere efficiente, sicuro, selettivo, penetrante. Infine, a seconda della patologia, dobbiamo capire se risulta maggiormente conveniente intervenire direttamente in cells and tissues of the patient (in vivo) or if "treated" by the isolated cells, cultured in the laboratory and then reinserted (Ex vivo). The choice of carrier depends on the length of the genetic code to be inserted, the type of target tissue, the quantity, quality and durability of the expression to be obtained for the gene in question. In ex-vivo gene therapy vectors can be used as physical electroporation and microinjection, but also liposomes, lipid vesicles that can serve as "boxes" of transport. However, are the most commonly used viral vectors. Viruses are naturally capable of delivering nucleic acids and insert into the cell and this quality makes them ideal for gene therapy, especially in vivo. They are designed to be inactive, individuals of viral genes, which are inserted in place of the genes of therapeutic interest, to be administered to the patient.
All this, however, is not enough.
The efficiency of transfer and the clinical outcome is proportional to the position in which the genetic code we produce is inserted on the duration of expression and the body's immune reaction to the virus or transformed cell, in some cases could to limit the effectiveness of therapy. These factors are relevant: an incorrect position can not continue to read, stimulate oncogenes or deactivate other genes protectors, non-permanent expression, which is not transmitted to daughter cells, prevents the long-term therapeutic effect.
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In essence, there are numerous obstacles to be overcome to make it effective and safe this therapeutic technique. Much has been made, the technology was refined and great results are at the gate, if not already present in many children, before the incurably ill. Of course, the possibility of modifying the genetic makeup of the cell to correct errors that fuel disease and suffering is something incredibly exciting and stimulating. But we must pay attention to the risks that these New technologies can hide. First, a possible involvement of germ cells, which would transfer to the children of genetic manipulation implemented. Secondly, but not in second order, the appropriation of these methods by biopolitical bodies, inspired and motivated by eugenic deviance, as was done in the past, selecting a superior race.
Massimiliano Fanni Canelles
