Nucleic acids (NA) therapies, including therapy with genes, aptamers or antisense oligonucleotides,
have been showing promising results, especially in the treatment of severe diseases
(e.g. cancer and AIDS). Nevertheless, the full success of medical treatments requires efficient
achievement of the therapeutic target and also the safety and effectiveness of the pharmaceutical
system. NA are not very efficient when administered alone, which means that the use of appropriate
methods for in vivo transfection of these molecules into targeted cells is fundamental. Examples of these techniques are the use of viral and
non-viral vectors to transfer the NA to the cells nucleus. Despite viral vectors have been demonstrating superior effectiveness for NA transfer,
some drawbacks have been pointed out, which focused the research in the non-viral vectors. However, the development of effective NA
delivery systems remains a challenge for pharmaceutical technologists, mainly because of their in vivo failure, which hinders their clinical
In this review article we address the characteristics of NA molecules and their respective limitations for formulation and administration.
An update on the state of the art related to the latest and outstanding developments from the in vivo applications of NA viral and non-viral
delivery systems is also presented. From this review, we can conclude that there is a lack of research regarding pre-clinical studies in specific
animal models of disease, which is required for further human clinical trials and for their use in clinics.