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Article Dans Une Revue Current Alzheimer Research Année : 2015

Improved brain expression of anti-amyloid β scFv by complexation of mRNA including a secretion sequence with PEG-based block catiomer

Federico Perche
Satoshi Uchida
Hiroki Akiba
  • Fonction : Auteur
Chin-Yu Lin
  • Fonction : Auteur
Masaru Ikegami
  • Fonction : Auteur
Anjaneyulu Dirisala
  • Fonction : Auteur
Toshihiro Nakashima
  • Fonction : Auteur
Keiji Itaka
  • Fonction : Auteur
Kohei Tsumoto
  • Fonction : Auteur
Kazunori Kataoka
  • Fonction : Auteur

Résumé

Amyloid β aggregates have been proposed as central effectors in Alzheimer's disease, with several passive immunization clinical trials. We used mRNA encoding oligomer-specific anti-amyloid β (Aβ) scFv for passive immunotherapy. These scFvs could recognize amyloid oligomers with significant affinity, delay the aggregation of amyloid β in vitro, and dissociate Aβ aggregates in vitro. Intra-cerebroventricular injection of pDNA and mRNA encoding the scFv resulted in detectable scFv levels in the brain, with higher in vivo expression from mRNA. Notably, injection of mRNA decreased Aβ burden in an acute amyloidosis model. scFv production in situ from mRNA represents a novel immunotherapy approach, and a safer alternative compared to the administration of anti-Aβ antibodies or adenovirus encoding antibodies.
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Dates et versions

hal-02995714 , version 1 (09-11-2020)

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Citer

Federico Perche, Satoshi Uchida, Hiroki Akiba, Chin-Yu Lin, Masaru Ikegami, et al.. Improved brain expression of anti-amyloid β scFv by complexation of mRNA including a secretion sequence with PEG-based block catiomer. Current Alzheimer Research, 2015, 1 (999), pp.1-1. ⟨10.2174/1567205013666161108110031⟩. ⟨hal-02995714⟩
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