Details

Autor(en) / Beteiligte

• Pardi, Norbert
• Secreto, Anthony J
• Shan, Xiaochuan
• Debonera, Fotini
• Glover, Joshua
• Yi, Yanjie
• Muramatsu, Hiromi
• Ni, Houping
• Mui, Barbara L
• Tam, Ying K
• Shaheen, Farida
• Collman, Ronald G
• Karikó, Katalin
• Danet-Desnoyers, Gwenn A
• Madden, Thomas D
• Hope, Michael J
• Weissman, Drew

Titel

Administration of nucleoside-modified mRNA encoding broadly neutralizing antibody protects humanized mice from HIV-1 challenge

Ist Teil von

• Nature communications, 2017-03, Vol.8 (1), p.14630-8, Article 14630

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2017

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Monoclonal antibodies are one of the fastest growing classes of pharmaceutical products, however, their potential is limited by the high cost of development and manufacturing. Here we present a safe and cost-effective platform for in vivo expression of therapeutic antibodies using nucleoside-modified mRNA. To demonstrate feasibility and protective efficacy, nucleoside-modified mRNAs encoding the light and heavy chains of the broadly neutralizing anti-HIV-1 antibody VRC01 are generated and encapsulated into lipid nanoparticles. Systemic administration of 1.4 mg kg of mRNA into mice results in ∼170 μg ml VRC01 antibody concentrations in the plasma 24 h post injection. Weekly injections of 1 mg kg of mRNA into immunodeficient mice maintain trough VRC01 levels above 40 μg ml . Most importantly, the translated antibody from a single injection of VRC01 mRNA protects humanized mice from intravenous HIV-1 challenge, demonstrating that nucleoside-modified mRNA represents a viable delivery platform for passive immunotherapy against HIV-1 with expansion to a variety of diseases.