Details

Autor(en) / Beteiligte

• Kuhlmann, Matthias
• Hamming, Jonas B.R.
• Voldum, Anders
• Tsakiridou, Georgia
• Larsen, Maja T.
• Schmøkel, Julie S.
• Sohn, Emil
• Bienk, Konrad
• Schaffert, David
• Sørensen, Esben S.
• Wengel, Jesper
• Dupont, Daniel M.
• Howard, Kenneth A.

Titel

An Albumin-Oligonucleotide Assembly for Potential Combinatorial Drug Delivery and Half-Life Extension Applications

Ist Teil von

• Molecular therapy. Nucleic acids, 2017-12, Vol.9 (C), p.284-293

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2017

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• The long blood circulatory property of human serum albumin, due to engagement with the cellular recycling neonatal Fc receptor (FcRn), is an attractive drug half-life extension enabling technology. This work describes a novel site-specific albumin double-stranded (ds) DNA assembly approach, in which the 3′ or 5′ end maleimide-derivatized oligodeoxynucleotides are conjugated to albumin cysteine at position 34 (cys34) and annealed with complementary strands to allow single site-specific protein modification with functionalized ds oligodeoxynucleotides. Electrophoretic gel shift assays demonstrated successful annealing of complementary strands bearing Atto488, 6-carboxyfluorescein (6-FAM), or a factor IXa aptamer to the albumin-oligodeoxynucleotide conjugate. A fluorometric factor IXa activity assay showed retained aptamer inhibitory activity upon assembly with the albumin and completely blocked factor IXa at a concentration of 100 nM for 2 hr. The assembled construct exhibited stability in serum-containing buffer and FcRn engagement that could be increased using an albumin variant engineered for higher FcRn affinity. This work presents a novel albumin-oligodeoxynucleotide assembly technology platform that offers potential combinatorial drug delivery and half-life extension applications.