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Over the past decades, non-viral DNA and RNA delivery systems have been intensively studied as an alternative to viral vectors. Despite the most significant advantage over viruses, such as the lack of immunogenicity and cytotoxicity, the widespread use of non-viral carriers in clinical practice is still limited due to the insufficient efficacy associated with the difficulties of overcoming extracellular and intracellular barriers. Overcoming barriers by non-viral carriers is facilitated by their chemical structure, surface charge, as well as developed modifications. Currently, there are many different forms of non-viral carriers for various applications. This review aimed to summarize recent developments based on the essential requirements for non-viral carriers for gene therapy.

Currently, gene therapy is considered as a potentially universal approach to the treatment of a wide range of diseases, such as cancer, cardiovascular diseases, diabetes, inherited diseases, and many others. It is known that "naked" nucleic acid is not able to effectively overcome the extraand intracellular barriers to reach the target cell, since it is easily degraded. In this regard, it becomes necessary to create special delivery vehicles. We investigated the modular arginine-rich cysteine-flanked polycondensed carriers stabilized by anionic glutamic acid-rich peptides. Glutamic acid-rich peptides can give colloidal stability of the studied complexes and protect them from interaction with negatively charged components of blood serum. Physicochemical, toxic, and transfection properties of the investigated complexes with siRNA were studied in cancer cell line MDA-MB-231-GFP + . Condensation analysis showed that the complexes with optimal charge ratios are not destroyed by the addition of anionic peptides. Also these polyplexes were stable in the serum-containing culture medium during cell transfection and nontoxic for the cells. Moreover, we measured the average size and zeta-potential of the siRNAnucleopeptide complexes. Based on this study, it was concluded that the complexes are capable of stably bind siRNA and have a high transfection efficiency in an optimal charge ratio, which provides new opportunities for the use of these carriers for siRNA delivery in vivo.