title: RALA-mediated delivery of FKBPL nucleic acid therapeutics.
abstract: OBJECTIVE
  RALA is a novel 30 mer bioinspired amphipathic peptide that is showing promise for gene delivery. Here, we used RALA to deliver the FK506-binding protein like - FKBPL gene (pFKBPL) - a novel member of the immunophilin protein family. FKBPL is a secreted protein, with overexpression shown to inhibit angiogenesis, tumor growth and stemness, through a variety of intra- and extracellular signaling mechanisms. We also elucidated proangiogenic activity and stemness after utilizing RALA to deliver siRNA (siFKBPL).
  
  
  METHODS
  The RALA/pFKBPL and RALA/siFKBPL nanoparticles were characterized in terms of size, charge, stability and toxicity. Overexpression and knockdown of FKBPL was assessed in vitro and in vivo.
  
  
  RESULTS
  RALA delivered both pFKBPL and siFKBPL with less cytotoxicity than commercially available counterparts. In vivo, RALA/pFKBPL delivery retarded tumor growth, and prolonged survival with an associated decrease in angiogenesis, while RALA/siFKBPL had no effect on tumor growth rate or survival, but resulted in an increase in angiogenesis and stemness.
  
  
  CONCLUSIONS
  RALA is an effective delivery system for both FKBPL DNA and RNAi and highlights an alternative therapeutic approach to harnessing FKBPL's antiangiogenic and antistemness activity.
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Bennett
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland, UK.
authors.forename: Anita
authors.initials: A
authors.lastname: Yakkundi
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland, UK.
authors.forename: Hayley D
authors.initials: HD
authors.lastname: McKeen
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland, UK.
authors.forename: Lana
authors.initials: L
authors.lastname: McClements
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland, UK.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: McKeogh
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland, UK.
authors.forename: Cian M
authors.initials: CM
authors.lastname: McCrudden
authors.affiliation: Northern Ireland Molecular Pathology Laboratory, Queen's University Belfast, Belfast, BT9 7BL, Northern Ireland, UK.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Arthur
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland, UK.
authors.forename: Tracy
authors.initials: T
authors.lastname: Robson
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland, UK.
authors.forename: Helen O
authors.initials: HO
authors.lastname: McCarthy
keywords: FKBPL DNA; RALA peptide; RNAi; antiangiogenic; nanoparticle