Novel materials from protein–polymer grafts

Kaleem, K.; Erhan, Semih; Chertok, F.

doi:10.1038/325328a0

Cited by 21 publications

(6 citation statements)

References 8 publications

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“…KIF5B exons 1–15 comprise the kinesin motor and coiled-coil domains that mediate homodimerization, whereas exon 15 is a known KIF5B-ALK fusion site in individuals with NSCLC 18 . RET exons 12–20 encode the tyrosine kinase portion of the PTC-RET fusions observed in ~35% of papillary thyroid carcinomas 19 (Fig. 2c).…”

mentioning

confidence: 99%

Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies

Lipson¹,

Capelletti

Yelensky³

et al. 2012

Nat Med

770

653

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Applying a next-generation sequencing assay targeting 145 cancer-relevant genes in 40 colorectal cancer and 24 non–small cell lung cancer formalin-fixed paraffin-embedded tissue specimens identified at least one clinically relevant genomic alteration in 59% of the samples and revealed two gene fusions, C2orf44-ALK in a colorectal cancer sample and KIF5B-RET in a lung adenocarcinoma. Further screening of 561 lung adenocarcinomas identified 11 additional tumors with KIF5B-RET gene fusions (2.0%; 95% CI 0.8–3.1%). Cells expressing oncogenic KIF5B-RET are sensitive to multi-kinase inhibitors that inhibit RET.

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mentioning

confidence: 99%

Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies

Lipson¹,

Capelletti

Yelensky³

et al. 2012

Nat Med

770

653

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“…The joining of natural and unnatural polymers is a powerful way to make macromolecules with unique properties, 1−5 and protein–polymer hybrids (PPHs) are therefore finding growing use in the field of biomedicine. Coatings of polyethylene glycol (PEG) have long been employed to provide enhanced solubility and reduced immunogenicity to protein therapeutics.…”

mentioning

confidence: 99%

Encapsidated Atom-Transfer Radical Polymerization in Qβ Virus-like Nanoparticles

et al. 2014

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Virus-like particles (VLPs) are unique macromolecular structures that hold great promise in biomedical and biomaterial applications. The interior of the 30 nm-diameter Qβ VLP was functionalized by a three-step process: (1) hydrolytic removal of endogenously packaged RNA, (2) covalent attachment of initiator molecules to unnatural amino acid residues located on the interior capsid surface, and (3) atom-transfer radical polymerization of tertiary amine-bearing methacrylate monomers. The resulting polymer-containing particles were moderately expanded in size; however, biotin-derivatized polymer strands were only very weakly accessible to avidin, suggesting that most of the polymer was confined within the protein shell. The polymer-containing particles were also found to exhibit physical and chemical properties characteristic of positively charged nanostructures, including the ability to easily enter mammalian cells and deliver functional small interfering RNA.

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“…The covalent attachment of hydrophilic polymer chains to the surface of biomolecules and nanoparticles has allowed for the development of hybrid macromolecular assemblies with unique properties that are finding increased use in the field of biomedicine. − Conjugation of linear poly(ethylene glycol) (PEG) has been widely used to dampen the immunogenicity of proteins and other materials, , and all of the protein–polymer hybrid drugs currently approved by the FDA are PEGylated conjugates . Furthermore, attached polymers have been shown to improve the circulation lifetime of proteins, which is a critical factor for advancing protein-based therapeutics into the clinic. − Protein–polymer hybrids are typically generated using either “grafting-to” , or “grafting-from” , methodologies.…”

Section: Introductionmentioning

confidence: 99%

Immunological Properties of Protein–Polymer Nanoparticles

Crooke¹,

Zheng

Ganewatta

et al. 2018

ACS Appl. Bio Mater.

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The covalent attachment of polymers to the surface of proteins and nanoparticles has been widely employed in the development of biomedical platforms capable of delaying or diminishing immune surveillance. The most widely employed polymer for these applications has been poly(ethylene glycol) (PEG), yet recent evidence has suggested that other polymer architectures and compositions provide significantly better in vitro and in vivo properties of protein–polymer hybrid materials. Moreover, few direct comparisons of PEG to these polymers have been reported. Here we describe the assembly and characterization of a series of polymer conjugates of a representative immunogenic viruslike particle (VLP) using (poly(oligo(ethylene glycol) methacrylate), poly(methacrylamido glucopyranose), and PEG, and an investigation of their ability to shield the protein from antibody recognition as a function of polymer loading density, chain length, architecture, and conjugation site. Increasing chain length and loading density were both found to significantly diminish antibody recognition of the VLP conjugates; the conformation adopted by different polymer architectures was also found to greatly influence antibody recognition. A direct comparison of these conjugates to PEGylated VLPs in vivo showed that all formulations gave rise to similar antibody titers that were significantly diminished relative to unmodified particles. Interestingly, the quality of the antibody response was impacted by the properties of the conjugate, with differences in observed affinity and avidity suggesting a complex dependence on loading density, chain length, and architecture.

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Novel materials from protein–polymer grafts

Cited by 21 publications

References 8 publications

Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies

Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies

Encapsidated Atom-Transfer Radical Polymerization in Qβ Virus-like Nanoparticles

Immunological Properties of Protein–Polymer Nanoparticles

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