Non-Viral Gene Delivery Utilizing RALA Modulates sFlt-1 Secretion, Important for Preeclampsia

McNally, Ross; Alqudah, Abdelrahim; McErlean, Emma; Rennie, Claire; Morshed, Nabila; Short, Amy; McGrath, Kristine; Shimoni, Olga; Robson, Tracy; McCarthy, Helen; McClements, Lana

doi:10.2217/nnm-2021-0180

Cited by 3 publications

(1 citation statement)

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“…In addition to the immunosuppressant effects, immunophilins have shown to have important roles in inflammation [ 21 ], cancer [ 22 ], cardiovascular disease and neurodegenerative disorders [ 23 – 25 ], by regulating soluble protein retrotransport through the interaction with dynein motors [ 4 ], neurodifferentiation and neuroregeneration [ 26 ], adipocytes differentiation [ 27 ], transcriptional regulation [ 28 ], steroid binding capacity [ 29 ], cell division [ 30 ] and apoptosis [ 31 ]. Even though fibrosis develops as a sequela of inflammation, the role of immunophilins in the process of fibrosis development has not yet been elucidated.…”

Section: Introductionmentioning

confidence: 99%

The emerging importance of immunophilins in fibrosis development

et al. 2022

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Immunophilins are a family of proteins encompassing FK506-binding proteins (FKBPs) and cyclophilins (Cyps). FKBPs and Cyps exert peptidyl-prolyl cis-trans isomerase (PPIase) activity, which facilitates diverse protein folding assembly, or disassembly. In addition, they bind to immunosuppressant medications where FKBPs bind to tacrolimus (FK506) and rapamycin, whereas cyclophilins bind to cyclosporin. Some large immunophilins have domains other than PPIase referred to as tetratricopeptide (TPR) domain, which is involved in heat shock protein 90 (Hsp90) and heat shock protein 70 (Hsp 70) chaperone interaction. The TPR domain confers immunophilins’ pleotropic actions to mediate various physiological and biochemical processes. So far, immunophilins have been implicated to play an important role in pathophysiology of inflammation, cancer and neurodegenerative disorders. However, their importance in the development of fibrosis has not yet been elucidated. In this review we focus on the pivotal functional and mechanistic roles of different immunophilins in fibrosis establishment affecting various organs. The vast majority of the studies reported that cyclophilin A, FKBP12 and FKBP10 likely induce organ fibrosis through the calcineurin or TGF-β pathways. FKBP51 demonstrated a role in myelofibrosis development through calcineurin-dependant pathway, STAT5 or NF-κB pathways. Inhibition of these specific immunophilins has been shown to decrease the extent of fibrosis suggesting that immunophilins could be a novel promising therapeutic target to prevent or reverse fibrosis.

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Section: Introductionmentioning

confidence: 99%

The emerging importance of immunophilins in fibrosis development

et al. 2022

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Maternal Gene Delivery for the Prevention and Treatment of Obstetric Conditions

D’Alessandro,

Boyle

2024

Curr Stem Cell Rep

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Purpose of Review There is an urgent unmet clinical need for effective therapies for obstetric complications such as fetal growth restriction, pre-eclampsia and preterm birth. These global health conditions have long term consequences for the health of survivors and the families affected, as well as societal and economic implications. Despite decades of research, prevention and treatment options are limited and often demonstrate suboptimal efficacy. Thus, cutting-edge approaches, such as gene delivery, may offer a novel solution. With the advancement of prenatal gene therapy preclinical research for the treatment of inherited diseases, the safe delivery of these technologies in utero is becoming a reality. Recent Findings We will give insights into the current preclinical research specifically relating to maternal gene delivery to improve the outcomes of pregnancy-related conditions. Summary Obstetric disorders lack effective prevention and treatment options. Innovative approaches, such as gene transfer, may provide a promising alternative. This review summarises potential gene therapies in preclinical development for fetal growth restriction, pre-eclampsia and preterm birth.

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