Selection and Modelling of a New Single-Domain Intrabody Against TDP-43

Martina Gilodi, Simonetta Lisi, Erika F. Dudas, Marco Fantini, Rita Puglisi, Alexandra Louka, Paolo Mercantili, Antonino Cattaneo*, Annalisa Pastore*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder associated to deteriorating motor and cognitive functions, and short survival. The disease is caused by neuronal death which results in progressive muscle wasting and weakness, ultimately leading to lethal respiratory failure. The misbehaviour of a specific protein, TDP-43, which aggregates and becomes toxic in ALS patient’s neurons, is supposed to be one of the causes. TDP-43 is a DNA/RNA-binding protein involved in several functions related to nucleic acid metabolism. Sequestration of TDP-43 aggregates is a possible therapeutic strategy that could alleviate or block pathology. Here, we describe the selection and characterization of a new intracellular antibody (intrabody) against TDP-43 from a llama nanobody library. The structure of the selected intrabody was predicted in silico and the model was used to suggest mutations that enabled to improve its expression yield, facilitating its experimental validation. We showed how coupling experimental methodologies with in silico design may allow us to obtain an antibody able to recognize the RNA binding regions of TDP-43. Our findings illustrate a strategy for the mitigation of TDP-43 proteinopathy in ALS and provide a potential new tool for diagnostics.
Original languageEnglish
Article number773234
JournalFrontiers in Molecular Biosciences
Early online date14 Feb 2022
Publication statusPublished - 14 Feb 2022


Dive into the research topics of 'Selection and Modelling of a New Single-Domain Intrabody Against TDP-43'. Together they form a unique fingerprint.

Cite this