Current state of in vivo panning technologies: Designing specificity and affinity into the future of drug targeting

Gustafson, Heather H.; Olshefsky, Audrey; Sylvestre, Meilyn; Sellers, Drew L.; Pun, Suzie H.

doi:10.1016/j.addr.2018.06.015

Cited by 16 publications

(19 citation statements)

References 123 publications

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“…Nanocarriers capable of the potent delivery of therapeutic molecules play a pivotal role in enhancing their therapeutic efficacy in clinic, and typically aid in minimizing systemic toxicity, improving biostability/bioavailability, and strengthening delivery efficiency to targeted tissues, cells, or subcellular locations (Savjani et al, 2012;Huang et al, 2013;Din et al, 2017;Gustafson et al, 2018;Zhang R. et al, 2019). Enormous progress has been made in this area, accompanied by the evolution of a large diversity of nanomaterials.…”

Section: Introductionmentioning

confidence: 99%

Rationally Designed DNA Nanostructures for Drug Delivery

Xia

Wang

2020

Front. Chem.

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DNA is an excellent biological material that has received growing attention in the field of nanotechnology due to its unique capability for precisely engineering materials via sequence specific interactions. Self-assembled DNA nanostructures of prescribed physicochemical properties have demonstrated potent drug delivery efficiency in vitro and in vivo. By using various conjugation techniques, DNA nanostructures may be precisely integrated with a large diversity of functional moieties, such as targeting ligands, proteins, and inorganic nanoparticles, to enrich their functionalities and to enhance their performance. In this review, we start with introducing strategies on constructing DNA nanostructures. We then summarize the biological barriers ahead of drug delivery using DNA nanostructures, followed by introducing existing rational solutions to overcome these biological barriers. Lastly, we discuss challenges and opportunities for DNA nanostructures toward real applications in clinical settings.

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Section: Introductionmentioning

confidence: 99%

Rationally Designed DNA Nanostructures for Drug Delivery

Xia

Wang

2020

Front. Chem.

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“…Bacteriophage M13K07 has been used in standard approaches for biopanning against purified proteins 12,13 and even in living animals. 14 Lerner's group combined yeast surface display with bacteriophage biopanning. They investigated methodology where a library of single-chain variable fragment (scFv) antibodies exposed on yeast cells was panned against a cDNA library displayed on phage particles to generate cognate pairs.…”

Section: ■ Introductionmentioning

confidence: 99%

Probing Surface Membrane Receptors Using Engineered Bacteriophage Bioconjugates

et al. 2019

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Specific recognition of ligands by surface receptors of eukaryotic cells is a fundamental process in sensing of the exogenous environment, including cell-to-cell communication. These interactions are therefore widely probed in both basic studies and drug development to enhance or interrupt them. Here, we designed a high-throughput publicly available platform for visualization and selection of eukaryotic cells according to the specificity of surface-exposed receptors by consolidation of phage display and flow cytometry techniques. Polypeptide ligands for membrane receptors are incorporated into every copy of p3 protein of M13K07 bacteriophage, which is intracellularly biotinylated to further accept PE-Cy7-labled streptavidin. Transgenic antigen-specific B-cells expressing membrane-tethered lymphoid B-cell receptor in a single-chain format interacted with engineered bacteriophages exposing the polypeptide ligand with an unprecedented selectivity of 97% and a false-positive detection value of 2.0%. Multivalent binding of the phage bioconjugates with the receptor provided significantly better specificity and sensitivity allowing application of engineered bacteriophage bioconjugates at a concentration 3 orders of magnitude lower in comparison with synthetic biotinylated peptide. We suggest that the platform described in this work may be applied either for routine staining or characterization of orphan membrane receptors exposed on the surface of living mammalian cells in their native environment.

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“…The real advantage of these libraries, however, is that they can be used for biopanning (reviewed in [ 366 ]), which is a method to screen phage libraries against immobilized antigen on plates or beads, cell-based screenings, tissue-based screenings and/or in vivo screenings. Using scFv phage libraries Edwards and colleagues identified a set of antibodies binding to the cell surface of human adipocytes [ 367 ].…”

Section: Chasing Adipose Selective Drug Deliverymentioning

confidence: 99%

“…Furthermore, targeting the adipose vasculature allowed the delivery of functional peptides and liposome into the adipose intercellular space [40,[369][370][371][372][373], suggesting that the surfome of the endothelium could also be a promising target in adipose tissue. Importantly, in vivo biopanning is not limited to phages but can be also performed with other 'barcoded'/retrievable molecules such as aptamers [366].…”

Section: Selecting Adipose Tissue Targeting Reagentsmentioning

confidence: 99%

Identification and characterization of adipose surface epitopes

Onogi

Khalil

Ussar

2020

Biochemical Journal

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Adipose tissue is a central regulator of metabolism and an important pharmacological target to treat the metabolic consequences of obesity, such as insulin resistance and dyslipidemia. Among the various cellular compartments, the adipocyte cell surface is especially appealing as a drug target as it contains various proteins that when activated or inhibited promote adipocyte health, change its endocrine function and eventually maintain or restore whole-body insulin sensitivity. In addition, cell surface proteins are readily accessible by various drug classes. However, targeting individual cell surface proteins in adipocytes has been difficult due to important functions of these proteins outside adipose tissue, raising various safety concerns. Thus, one of the biggest challenges is the lack of adipose selective surface proteins and/or targeting reagents. Here, we discuss several receptor families with an important function in adipogenesis and mature adipocytes to highlight the complexity at the cell surface and illustrate the problems with identifying adipose selective proteins. We then discuss that, while no unique adipocyte surface protein might exist, how splicing, posttranslational modifications as well as protein/protein interactions can create enormous diversity at the cell surface that vastly expands the space of potentially unique epitopes and how these selective epitopes can be identified and targeted.

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Current state of in vivo panning technologies: Designing specificity and affinity into the future of drug targeting

Cited by 16 publications

References 123 publications

Rationally Designed DNA Nanostructures for Drug Delivery

Rationally Designed DNA Nanostructures for Drug Delivery

Probing Surface Membrane Receptors Using Engineered Bacteriophage Bioconjugates

Identification and characterization of adipose surface epitopes

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