Type

Journal Article

Authors

Sally-Ann Cryan
Andreas Heise
Fergal J O'Brien
Jeremy C Simpson
Brenton Cavanagh
Rosanne M Raftery
Angela Panarella
Robert D Murphy
David P Walsh

Subjects

Biochemistry

Topics
bone morphogenetic protein 2 tissue engineering mesenchymal stem cells gene therapy stem cells genes reporter live cell imaging vascular endothelial growth factor

Bioinspired Star-Shaped Poly(l-lysine) Polypeptides: Efficient Polymeric Nanocarriers for the Delivery of DNA to Mesenchymal Stem Cells. (2018)

Abstract The field of tissue engineering is increasingly recognizing that gene therapy can be employed for modulating in vivo cellular response thereby guiding tissue regeneration. However, the field lacks a versatile and biocompatible gene delivery platform capable of efficiently delivering transgenes to mesenchymal stem cells (MSCs), a cell type often refractory to transfection. Herein, we describe the extensive and systematic exploration of three architectural variations of star-shaped poly(l-lysine) polypeptide (star-PLL) with varying number and length of poly(l-lysine) arms as potential nonviral gene delivery vectors for MSCs. We demonstrate that star-PLL vectors are capable of self-assembling with pDNA to form stable, cationic nanomedicines. Utilizing high content screening, live cell imaging, and mechanistic uptake studies we confirm the intracellular delivery of pDNA by star-PLLs to MSCs is a rapid process, which likely proceeds via a clathrin-independent mechanism. We identify a star-PLL composition with 64 poly(l-lysine) arms and five l-lysine subunits per arm as a particularly efficient vector that is capable of delivering both reporter genes and the therapeutic transgenes bone morphogenetic protein-2 and vascular endothelial growth factor to MSCs. This composition facilitated a 1000-fold increase in transgene expression in MSCs compared to its linear analogue, linear poly(l-lysine). Furthermore, it demonstrated comparable transgene expression to the widely used vector polyethylenimine using a lower pDNA dose with significantly less cytotoxicity. Overall, this study illustrates the ability of the star-PLL vectors to facilitate efficient, nontoxic nucleic acid delivery to MSCs thereby functioning as an innovative nanomedicine platform for tissue engineering applications.
Collections Ireland -> Trinity College Dublin -> PubMed

Full list of authors on original publication

Sally-Ann Cryan, Andreas Heise, Fergal J O'Brien, Jeremy C Simpson, Brenton Cavanagh, Rosanne M Raftery, Angela Panarella, Robert D Murphy, David P Walsh

Experts in our system

1
Sally-Ann Cryan
Royal College of Surgeons in Ireland
Total Publications: 67
 
2
Andreas Heise
Dublin City University
Total Publications: 30
 
3
Fergal J O'Brien
Royal College of Surgeons in Ireland
Total Publications: 265
 
4
Jeremy C. Simpson
University College Dublin
Total Publications: 31
 
5
Brenton Cavanagh
Royal College of Surgeons in Ireland
Total Publications: 4
 
6
Rosanne Raftery
Royal College of Surgeons in Ireland
Total Publications: 9
 
7
Angela Panarella
University College Dublin
Total Publications: 5