The concept of developing vaccines based on nucleic acids

Zanimanje za razvojem cjepiva temeljenih na nukleinskim kiselinama pojavio se prije trideset godina, no zadnjih deset godina intenzivno se istražuju mogućnosti primjene takvih cjepiva za prevenciju infektivnih bolesti, terapiju tumora i genetičkih poremećaja. Razlog tolikoga interesa za njihovim razvojem jest velik potencijal ovih cjepiva. Osim što uzrokuju humoralni i stanični imunosni odgovor aktivacijom i T i B limfocita proces njihove proizvodnje je jednostavan te, nakon primjene, ne postoji opasnost od razvoja burne reakcije, pa čak i bolesti. Glavni nedostatak ovih cjepiva jest nedovoljna imunogenost odnosno stimulacija imunosnoga sustava. Smatra se da je nedovoljna imunogenost takvih cjepiva povezana s njihovom nestabilnošću i nedostatnom dostavom nukleinskih kiselina u stanice. Istraživanja su dovela do brojnih rješenja navedenih problema. Inkorporacijom nukleinskih kiselina u sustave koji su djelotvorni u njihovoj dostavi u stanice, povećava se sinteza antigena, a time i stimulacija imunosnoga sustava. Posebnim dizajniranjem i modifikacijom molekula nukleinskih kiselina, kao što je optimizacija kodona i modifikacija baza kod mRNA ili te dodatak adjuvanasa kod DNA, povećava se njihova stabilnost i imunogenost. Zahvaljujući ovim metodama danas je u tijeku velik broj kliničkih istraživanja koja bi vrlo brzo mogla dovesti do svakodnevne primjene ovih cjepiva u prevenciji i terapiji bolesti.Interest in the development of vaccines based on nucleic acids appeared thirty years ago, but in the last ten years their application has been intensive for the prevention of infectious diseases and therapy of cancer and genetic disorders. The reason for so much interest in their development is the great potential of these vaccines. In addition to causing a humoral and cellular immune response by activating both T and B lymphocytes, the process of their production is simple and, after application, there is no danger of developing a violent reaction or even disease. The main drawback of these vaccines is insufficient immunogenicity, i.e. stimulation of the immune system, which is due to instability and insufficient delivery of nucleic acids to cells due to a large amount of negative charge. To date, many solutions have been discovered that could solve this problem. By incorporating nucleic acids into systems that are effective in delivering them to cells, the synthesis of antigens increases, and thus the stimulation of the immune system. Special design and modification of nucleic acid molecules, such as codon optimization and base modification in mRNA, and the addition of adjuvants to DNA increase their stability and, also, immunogenicity. Thanks to these methods, a large number of clinical researches are in circulation today, which could very soon lead to the daily use of these vaccines in the prevention and treatment of diseases