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1. Protein scaffold-based multimerization of soluble ACE2 efficiently blocks SARS-CoV-2 infection in vitro and in vivo

Author

Kayabölen, Alişan; Akcan, Uğur; Özturan, Doğancan; Sahin, Gizem Nur; Pınarbaşı Değirmenci, Nareğ; Bayraktar, Canan; Soyler, Gizem; Sarayloo, Ehsan; Nurtop, Elif; Özer, Berna; Güney Esken, Gülen; Barlas, Tayfun; Doğan, Özlem (ORCID 0000-0002-6505-4582 & YÖK ID 170418); Karahüseyinoğlu, Serçin (ORCID 0000-0001-5531-2587 & YÖK ID 110772); Lack, Nathan Alan (ORCID 0000-0001-7399-5844 & YÖK ID 120842); Kaya, Mehmet (ORCID 0000-0001-8318-1350 & YÖK ID 10486); Albayrak, Cem; Can, Füsun (ORCID 0000-0001-9387-2526 & YÖK ID 103165); Solaroğlu, İhsan (ORCID 0000-0002-9472-1735 & YÖK ID 102059); Önder, Tuğba Bağcı (ORCID 0000-0003-3646-2613 & YÖK ID 184359), Ulbegi Polat, Hivda; Yıldırım, İsmail Selim, Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), Koç University Hospital, Graduate School of Health Sciences; School of Medicine, Kayabölen, Alişan; Akcan, Uğur; Özturan, Doğancan; Sahin, Gizem Nur; Pınarbaşı Değirmenci, Nareğ; Bayraktar, Canan; Soyler, Gizem; Sarayloo, Ehsan; Nurtop, Elif; Özer, Berna; Güney Esken, Gülen; Barlas, Tayfun; Doğan, Özlem (ORCID 0000-0002-6505-4582 & YÖK ID 170418); Karahüseyinoğlu, Serçin (ORCID 0000-0001-5531-2587 & YÖK ID 110772); Lack, Nathan Alan (ORCID 0000-0001-7399-5844 & YÖK ID 120842); Kaya, Mehmet (ORCID 0000-0001-8318-1350 & YÖK ID 10486); Albayrak, Cem; Can, Füsun (ORCID 0000-0001-9387-2526 & YÖK ID 103165); Solaroğlu, İhsan (ORCID 0000-0002-9472-1735 & YÖK ID 102059); Önder, Tuğba Bağcı (ORCID 0000-0003-3646-2613 & YÖK ID 184359), Ulbegi Polat, Hivda; Yıldırım, İsmail Selim, Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), Koç University Hospital, and Graduate School of Health Sciences; School of Medicine

Abstract

Soluble ACE2 (sACE2) decoys are promising agents to inhibit SARS-CoV-2, as their efficiency is unlikely to be affected by escape mutations. However, their success is limited by their relatively poor potency. To address this challenge, multimeric sACE2 consisting of SunTag or MoonTag systems is developed. These systems are extremely effective in neutralizing SARS-CoV-2 in pseudoviral systems and in clinical isolates, perform better than the dimeric or trimeric sACE2, and exhibit greater than 100-fold neutralization efficiency, compared to monomeric sACE2. SunTag or MoonTag fused to a more potent sACE2 (v1) achieves a sub-nanomolar IC50, comparable with clinical monoclonal antibodies. Pseudoviruses bearing mutations for variants of concern, including delta and omicron, are also neutralized efficiently with multimeric sACE2. Finally, therapeutic treatment of sACE2(v1)-MoonTag provides protection against SARS-CoV-2 infection in an in vivo mouse model. Therefore, highly potent multimeric sACE2 may offer a promising treatment approach against SARS-CoV-2 infections., Koç University Isbank Center for Infectious Diseases (KUISCID); Koç University Research Center for Transla-tional Medicine (KUTTAM)

Published
2022

2. Neovascularization of engineered tissues for clinical translation: where we are, where we should be?

Author

Nazeer, Muhammad Anwaar; Karaoğlu, İsmail Can; Albayrak, Cem; Kızılel, Seda (ORCID 0000-0001-9092-2698 & YÖK ID 28376); Özer, Onur, Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), Graduate School of Sciences and Engineering; College of Engineering, Department of Chemical and Biological Engineering; Department of Biomedical Sciences and Engineering, Nazeer, Muhammad Anwaar; Karaoğlu, İsmail Can; Albayrak, Cem; Kızılel, Seda (ORCID 0000-0001-9092-2698 & YÖK ID 28376); Özer, Onur, Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), Graduate School of Sciences and Engineering; College of Engineering, and Department of Chemical and Biological Engineering; Department of Biomedical Sciences and Engineering

Abstract

One of the key challenges in engineering three-dimensional tissue constructs is the development of a mature microvascular network capable of supplying sufficient oxygen and nutrients to the tissue. Recent angiogenic therapeutic strategies have focused on vascularization of the constructed tissue, and its integration in vitro; these strategies typically combine regenerative cells, growth factors (GFs) with custom-designed biomaterials. However, the field needs to progress in the clinical translation of tissue engineering strategies. The article first presents a detailed description of the steps in neovascularization and the roles of extracellular matrix elements such as GFs in angiogenesis. It then delves into decellularization, cell, and GF-based strategies employed thus far for therapeutic angiogenesis, with a particularly detailed examination of different methods by which GFs are delivered in biomaterial scaffolds. Finally, interdisciplinary approaches involving advancement in biomaterials science and current state of technological development in fabrication techniques are critically evaluated, and a list of remaining challenges is presented that need to be solved for successful translation to the clinics., Scientific and Technological Research Council of Turkey (TÜBİTAK); ARDEB 1001 Scientific and Technological Research Projects Funding Program; 3501 National Young Researchers Career Development Program; Koç University Seed Fund

Published
2021

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