AAV-delivered anti-PrPC nanobodies (Nb196, Nb484, Nb862)

Nanobodies are small single-domain binders derived from llama antibodies. Three that bind the normal prion protein (PrPC) were made to be produced inside the mouse brain from an AAV vector, to test whether they could slow prion disease. In the one published mouse study only Nb862 helped, and only by about 8 days on a survival of roughly 176 days; the other two did nothing measurable. The work is early preclinical research from Beijing, Michigan, Brussels and Houston. It is not Zurich work, and no human use exists. Information only.

Key facts

  • The in vivo study is Zhang et al, Pathogens 2025;14:131, with Jiyan Ma as corresponding author at Capital Medical University and the Chinese Institute for Brain Research, Beijing; coauthors are at Van Andel Institute, VIB-VUB Brussels and UTHealth Houston.
  • Nb196, Nb484 and Nb862 were delivered with rAAV-PHP.eB injected into the ventricles of newborn mice (3 x 10^10 genome copies), using a nanobody against GFP as control.
  • Expression was concentrated in olfactory bulb, cortex and hippocampus, stayed high to about 180 days except for Nb484, and no abnormalities were seen over more than 600 days.
  • Only Nb862 extended survival after prion inoculation: 176 +/- 1.9 to 184 +/- 1.8 days; first death moved from 166 to 180 days. The authors call this modest.
  • Protease-resistant PrP, spongiosis, astrogliosis and microgliosis were not reduced, so the mechanism is unclear; the authors suggest blocking PrPC-mediated toxicity and say higher nanobody levels are probably needed.
  • The text read gives no p-values for survival and does not name the prion or mouse strain.
  • Nb484 came from a llama immunised with recombinant mouse PrP, binds the hydrophobic region of PrP, blocked a recombinant prion system in vitro and was not toxic in brain slices where the antibody POM1 was.
  • Nb862 came from a llama immunised with PrPSc from scrapie-infected cells and binds PrP more tightly than Nb484, but did not inhibit propagation in the 2019 in vitro system.
  • The nanobodies originate from Steyaert (Brussels) and Ma and Wang (Van Andel Institute), not from Zurich; Aguzzi is cited only as background.
  • Funding was internal to the Beijing institute, with an early pilot supported by a CJD Foundation memorial grant.
  • A search found no clinical or primate work and only vendor pages beyond the papers.

Timeline

  1. 2019Abskharon et al publish the Nb484 structure with PrP and in vitro and slice data (PLoS Pathog).
  2. 2024Zhang et al submit the AAV nanobody paper (received 30 December).
  3. 2025Paper accepted on 23 January.
  4. 2025Published in Pathogens 14(2):131 on 2 February.

Last checked 1 November 2026

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