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Schissel, C. K.

Publications and source records attributed to Schissel, C. K..

2 recordsLinked to original sources
bioRxiv2020

Erythrocyte-targeted immunomodulatory antigens enabled by in vivo selection of D-peptides

Targeting of antigens to erythrocytes can be used to selectively mitigate their immunogenicity, but the methods to equip a variety of cargoes with erythrocyte-targeting properties are limited. Here we identified a D-peptide that targets murine erythrocytes and decreases anti-drug antibody responses when conjugated to the protective antigen from Bacillus anthracis, a protein of therapeutic interest. The D-peptide likewise decreases inflammatory anti-ovalbumin (OVA) CD8+ T cell responses when attached to a peptide antigen derived from OVA. To discover this targeting ligand, we leveraged mass spectrometry to decode a randomized D-peptide library selected in mice, extending the application of synthetic libraries to in vivo affinity selections.

bioengineering↗
bioRxiv2020

Interpretable Deep Learning for De Novo Design of Cell-Penetrating Abiotic Polymers

There are more amino acid permutations within a 40-residue sequence than atoms on Earth. This vast chemical search space hinders the use of human learning to design functional polymers. Here we couple supervised and unsupervised deep learning with high-throughput experimentation to drive the design of high-activity, novel sequences reaching 10 kDa that deliver antisense oligonucleotides to the nucleus of cells. The models, in which natural and unnatural residues are represented as topological fingerprints, decipher and visualize sequence-activity predictions. The new variants boost antisense activity by 50-fold, are effective in animals, are nontoxic, and can also deliver proteins into the cytosol. Machine learning can discover functional polymers that enhance cellular uptake of biotherapeutics, with significant implications toward developing therapies for currently untreatable diseases. One sentence summaryDeep learning generates de novo large functional abiotic polymers that deliver antisense oligonucleotides to the nucleus.

bioinformatics↗