**4. Conclusions**

Still nowadays most lysosomal storage disorders do not have an effective treatment. Moreover, treatments currently available are not able to correct all the manifestations of these multisystemic diseases. Despite the small number of protocols (if compared to other areas, like oncology), gene therapy approaches have shown their potential to be helpful in many of these diseases. Not only proof of concept experiments have been performed, but clinically relevant results were obtained in some cases.

The limitations of non-viral gene transfer, i.e., transient expression of the transgene and low transfection efficiency, are being slowly overcome in the last decade using improved vector design and techniques, such as nanotechnology, transposons, and minicircle approaches (to name a few) as demonstrated throughout this chapter. Novel mechanisms to help the DNA to escape endosomal degradation and pass through the nuclear envelope are also under development but were not in the scope of this chapter. Nevertheless, these improvements help non-viral gene therapy to move towards clinical trials in LSDs, which are expected to happen in the years to come. Non-viral vectors are safer than viral particles, which make them an appealing alternative for treatment of lysosomal storage disorders and even other monogenic diseases. Yet, there is a long way to clinical application but the road is paved and the scientific community advances steadily.
