Figure 3.

Molecular approaches for the use of miRNAs derived from TR exosomes as therapeutic tools.

Notes: Exosomes are ideal delivery systems that can be manipulated for the administration of specific molecules such as synthetic miRNAs or anti-miRNAs. (A) Synthetic miRNAs may be transfected into an exosome-producing cell (eg, mesenchymal stem cell). Transfected miRNAs are released and delivered to the recipient cell via exosomes. Once they reach the recipient cell, synthetic miRNAs bind and arrest the translation of their canonical target transcripts (1). MiRNAs can also act like ligands to activate membrane surface receptors (2). (B) In a similar strategy, anti-miRNA molecules are transfected into exosome-producing cells, where they reduce the levels of endogenous miRNAs in the donor cell, thus diminishing the amount of miRNAs transferred to the recipient cells. (C) Alternatively, anti-miRNA molecules can be directly transduced into exosomes and delivered to the recipient cell, where they prevent miRNAs from silencing their cognate mRNA. In a similar fashion, siRNA molecules can be employed to downregulate mRNA targets.

Abbreviations: miRNA, microRNA; mRNA, messenger RNA; MVB, multivesicular body; RISC, RNA-induced silencing complex; siRNA, short interfering RNA; TLR, toll-like receptor; TR, tumor-released; UTR, untranslated region.