In vivo nucleic acid delivery with PEI and its derivatives: current status and perspectives

Poly(ethylenimine) (PEI) has recently emerged as a favorable candidate for nucleic acid (NA) delivery because of its good effectivity at low cost. Despite copious derivatives and formulations being explored over the years, there is a scarcity of efforts to systematically review the current status and unmet needs of related research. The objective of this article is to fill this gap by revisiting the recent advances and challenges in in vivo NA delivery mediated by PEI. For this, related literature was retrieved from Pub Med and Web of Science, and among the 530 articles yielded, 49 recent in vivo studies were selected for further analysis. Based on the distillation of literature, implications for research will be drawn and prospects of PEI-mediated NA delivery for stem cell- and RNA-based therapies will be explored. It is hoped that this article could add a new insight to the field and to clinical endeavors in the future.