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ADAPT as a single-d...
ADAPT as a single-domain bispecific scaffold capable of albumin-associated haf-life extension for therapeutic applications
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- von Witting, Emma (författare)
- KTH,Proteinteknologi
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- Lindbo, Sarah (författare)
- KTH,Proteinteknologi
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- Lundqvist, Magnus (författare)
- KTH,Proteinteknologi
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- Möller, Marit (författare)
- KTH,Proteinteknologi
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- Wisniewski, Andreas (författare)
- KTH,Proteinteknologi
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- Kanje, Sara, 1986- (författare)
- KTH,Skolan för kemi, bioteknologi och hälsa (CBH)
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- Rockberg, Johan (författare)
- KTH,Proteinteknologi
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- Tegel, Hanna (författare)
- KTH,Proteinvetenskap
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- Åstrand, Mikael (författare)
- KTH,Albanova VinnExcellence Center for Protein Technology, ProNova
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- Uhlén, Mathias (författare)
- KTH,Science for Life Laboratory, SciLifeLab
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Hober, Sophia, 1965- (författare)
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(creator_code:org_t)
- Engelska.
- Relaterad länk:
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https://urn.kb.se/re...
Abstract
Ämnesord
Stäng
- Albumin-binding fusion partners are frequently used as a means for the in vivo half-life extension of small therapeutic molecules that would normally be cleared very rapidly from circulation. However, in applications where small size is key, fusion to an additional molecule can be disadvantageous. ABD-Derived Affinity ProTeins (ADAPTs) are a type of scaffold proteins based on one of the albumin binding domains of streptococcal Protein G, with newly introduced binding specificities against numerous targets. Here we engineered this scaffold further and showed that this domain, as small as 6 kDa, can harbor two distinct binding surfaces and utilize them to interact with two targets simultaneously. These novel ADAPTs were developed to bind to both serum albumin as well as another clinically relevant target, thus circumventing the need for an albumin binding fusion partner. To accomplish this, we designed a novel phage display library and used it to successfully select for single-domain bispecific binders towards a panel of targets: TNFa, PSA (Prostate Specific Antigen), CRP (C-reactive protein), renin, angiogenin and insulin. Apart from successfully identifying bispecific binders for all targets, we also demonstrated the formation of the ternary complex of the ADAPT together with albumin and each of the four targets TNFa, PSA, angiogenin and insulin. This simultaneous binding of albumin and other targets presents an opportunity to combine the advantages of small molecules with those of larger ones allowing for lower cost of goods and non-invasive administration routes while still maintaining a sufficient in vivo half-life.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Nyckelord
- Protein engineering
- phage display
- next generation sequencing
- ABD
- ADAPT
- albumin
- half-life extension
- Biotechnology
- Bioteknologi
Publikations- och innehållstyp
- vet (ämneskategori)
- ovr (ämneskategori)
- Av författaren/redakt...
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von Witting, Emm ...
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Lindbo, Sarah
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Lundqvist, Magnu ...
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Möller, Marit
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Wisniewski, Andr ...
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Kanje, Sara, 198 ...
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visa fler...
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Rockberg, Johan
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Tegel, Hanna
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Åstrand, Mikael
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Uhlén, Mathias
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Hober, Sophia, 1 ...
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinsk biotek ...
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och Medicinsk biotek ...
- Av lärosätet
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Kungliga Tekniska Högskolan