**Domenico Marson, Erik Laurini \*, Suzana Aulic, Maurizio Fermeglia and Sabrina Pricl**

Molecular Biology and Nanotechnology Laboratory (MolBNL@UniTS), Department of Engineering and Architecture, University of Trieste, 34127 Trieste, Italy

**\*** Correspondence: erik.laurini@dia.units.it; Tel.: +39-040-558-3432

Received: 21 June 2019; Accepted: 16 July 2019; Published: 18 July 2019

**Abstract:** Small interfering RNAs (siRNAs) represent a new approach towards the inhibition of gene expression; as such, they have rapidly emerged as promising therapeutics for a plethora of important human pathologies including cancer, cardiovascular diseases, and other disorders of a genetic etiology. However, the clinical translation of RNA interference (RNAi) requires safe and efficient vectors for siRNA delivery into cells. Dendrimers are attractive nanovectors to serve this purpose, as they present a unique, well-defined architecture and exhibit cooperative and multivalent effects at the nanoscale. This short review presents a brief introduction to RNAi-based therapeutics, the advantages offered by dendrimers as siRNA nanocarriers, and the remarkable results we achieved with bio-inspired, structurally flexible covalent dendrimers. In the companion paper, we next report our recent efforts in designing, characterizing and testing a series of self-assembled amphiphilic dendrimers and their related structural alterations to achieve unprecedented efficient siRNA delivery both in vitro and in vivo.

**Keywords:**RNAi therapeutics; siRNA delivery; covalent dendrimers; PAMAM dendrimers; nanovectors; gene silencing
