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. 2022 Apr 12;13:870799. doi: 10.3389/fneur.2022.870799

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Copyright © 2022 Marino and Holt.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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mAbs derivatives for A-MAD. (A) Representative scheme of a single-chain fragment variable (scFv) antibody fragment, derived from a human immunoglobulin. This class of engineered antibody is composed of the variable regions of the heavy (VH) and light chains (VL) fused by a linker. Their applicability is limited by potential folding and stability issues in the reducing environment of the cell. (B) Representative scheme of a VHH, the smallest antigen-binding functional fragment in nature, derived from a camelid immunoglobulin. The small size, high antigen specificity and exceptional stability of VHH (including in the reducing environment of the cell) make them an ideal cargo for rAAV vector-mediated delivery to target CNS proteinopathies.