Imperial College London
Alternate

ProfessorMatthewPickering

Faculty of Medicine, Department of Immunology and Inflammation

Centre Director, Professor of Rheumatology
 
 
 
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Contact

 

matthew.pickering Website

 
 
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Assistant

 

Miss Claudia Rocchi +44 (0)20 3313 2315

 
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Location

 

9N12Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Ahmad:2021:10.1089/hum.2021.022,
author = {Ahmad, A and Mandwie, M and Dreismann, AK and Smyth, C and Doyle, H and Malik, TH and Pickering, MC and Lachmann, PJ and Alexander, IE and Logan, G},
doi = {10.1089/hum.2021.022},
journal = {Human Gene Therapy},
pages = {1370--1381},
title = {Adeno-associated virus vector gene delivery elevates Factor I levels and down-regulates the complement alternative pathway in vivo.},
url = {http://dx.doi.org/10.1089/hum.2021.022},
volume = {32},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The complement system is a key component of innate immunity but impaired regulation influences disease susceptibility, including age-related macular degeneration (AMD) and some kidney diseases. Whilst complete complement inhibition has been used successfully to treat acute kidney disease, key unresolved challenges include strategies to modulate rather than completely inhibit the system and to deliver therapy potentially over decades. Elevating concentrations of complement regulator factor I (CFI) restricts complement activation in vitro and this approach was extended in the current study to modulate complement activation in vivo. Sustained increases in CFI levels were achieved using an adeno-associated virus (AAV) vector to target the liver, inducing a 4- to 5-fold increase in circulating CFI levels. This led to decreased activity of the alternative pathway as demonstrated by a reduction in the rate of iC3b deposition and more rapid formation of C3 degradation products. In addition, vector application in a mouse model of systemic lupus erythematosus (NZBWF1), where tissue injury is in part complement dependent, resulted in reduced complement C3 and IgG renal deposition. Collectively, these data demonstrate that sustained elevation of CFI reduces complement activation in vivo providing proof-of-principle support for the therapeutic application of AAV gene delivery to modulate complement activation.
AU  - Ahmad,A
AU  - Mandwie,M
AU  - Dreismann,AK
AU  - Smyth,C
AU  - Doyle,H
AU  - Malik,TH
AU  - Pickering,MC
AU  - Lachmann,PJ
AU  - Alexander,IE
AU  - Logan,G
DO  - 10.1089/hum.2021.022
EP  - 1381
PY  - 2021///
SN  - 1043-0342
SP  - 1370
TI  - Adeno-associated virus vector gene delivery elevates Factor I levels and down-regulates the complement alternative pathway in vivo.
T2  - Human Gene Therapy
UR  - http://dx.doi.org/10.1089/hum.2021.022
UR  - https://www.ncbi.nlm.nih.gov/pubmed/34238030
UR  - https://www.liebertpub.com/doi/10.1089/hum.2021.022
UR  - http://hdl.handle.net/10044/1/91246
VL  - 32
ER  -
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