A Methodological Approach Using rAAV Vectors Encoding Nanobody-Based Biologics to Evaluate ARTC2.2 and P2X7 In Vivo
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A Methodological Approach Using rAAV Vectors Encoding Nanobody-Based Biologics to Evaluate ARTC2.2 and P2X7 In Vivo. / Gondé, Henri; Demeules, Mélanie; Hardet, Romain; Scarpitta, Allan; Junge, Marten; Pinto-Espinoza, Carolina; Varin, Rémi; Koch-Nolte, Friedrich; Boyer, Olivier; Adriouch, Sahil.
In: FRONT IMMUNOL, Vol. 12, 704408, 2021.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - A Methodological Approach Using rAAV Vectors Encoding Nanobody-Based Biologics to Evaluate ARTC2.2 and P2X7 In Vivo
AU - Gondé, Henri
AU - Demeules, Mélanie
AU - Hardet, Romain
AU - Scarpitta, Allan
AU - Junge, Marten
AU - Pinto-Espinoza, Carolina
AU - Varin, Rémi
AU - Koch-Nolte, Friedrich
AU - Boyer, Olivier
AU - Adriouch, Sahil
N1 - Copyright © 2021 Gondé, Demeules, Hardet, Scarpitta, Junge, Pinto-Espinoza, Varin, Koch-Nolte, Boyer and Adriouch.
PY - 2021
Y1 - 2021
N2 - On murine T cells, mono-ADP ribosyltransferase ARTC2.2 catalyzes ADP-ribosylation of various surface proteins when nicotinamide adenine dinucleotide (NAD+) is released into the extracellular compartment. Covalent ADP-ribosylation of the P2X7 receptor by ARTC2.2 thereby represents an additional mechanism of activation, complementary to its triggering by extracellular ATP. P2X7 is a multifaceted receptor that may represents a potential target in inflammatory, and neurodegenerative diseases, as well as in cancer. We present herein an experimental approach using intramuscular injection of recombinant AAV vectors (rAAV) encoding nanobody-based biologics targeting ARTC2.2 or P2X7. We demonstrate the ability of these in vivo generated biologics to potently and durably block P2X7 or ARTC2.2 activities in vivo, or in contrast, to potentiate NAD+- or ATP-induced activation of P2X7. We additionally demonstrate the ability of rAAV-encoded functional heavy chain antibodies to elicit long-term depletion of T cells expressing high levels of ARTC2.2 or P2X7. Our approach of using rAAV to generate functional nanobody-based biologics in vivo appears promising to evaluate the role of ARTC2.2 and P2X7 in murine acute as well as chronic disease models.
AB - On murine T cells, mono-ADP ribosyltransferase ARTC2.2 catalyzes ADP-ribosylation of various surface proteins when nicotinamide adenine dinucleotide (NAD+) is released into the extracellular compartment. Covalent ADP-ribosylation of the P2X7 receptor by ARTC2.2 thereby represents an additional mechanism of activation, complementary to its triggering by extracellular ATP. P2X7 is a multifaceted receptor that may represents a potential target in inflammatory, and neurodegenerative diseases, as well as in cancer. We present herein an experimental approach using intramuscular injection of recombinant AAV vectors (rAAV) encoding nanobody-based biologics targeting ARTC2.2 or P2X7. We demonstrate the ability of these in vivo generated biologics to potently and durably block P2X7 or ARTC2.2 activities in vivo, or in contrast, to potentiate NAD+- or ATP-induced activation of P2X7. We additionally demonstrate the ability of rAAV-encoded functional heavy chain antibodies to elicit long-term depletion of T cells expressing high levels of ARTC2.2 or P2X7. Our approach of using rAAV to generate functional nanobody-based biologics in vivo appears promising to evaluate the role of ARTC2.2 and P2X7 in murine acute as well as chronic disease models.
KW - ADP Ribose Transferases/antagonists & inhibitors
KW - Animals
KW - Biological Products/immunology
KW - Dependovirus
KW - Genetic Vectors
KW - Lymphocyte Depletion
KW - Mice
KW - Receptors, Purinergic P2X7/immunology
KW - Single-Domain Antibodies/genetics
U2 - 10.3389/fimmu.2021.704408
DO - 10.3389/fimmu.2021.704408
M3 - SCORING: Journal article
C2 - 34489954
VL - 12
JO - FRONT IMMUNOL
JF - FRONT IMMUNOL
SN - 1664-3224
M1 - 704408
ER -
