Identification of malaria parasite-infected red blood cell surface aptamers by inertial microfluidic SELEX (I-SELEX)
Plasmodium falciparum malaria parasites invade and remodel human red blood cells (RBCs) by trafficking parasite-synthesized proteins to the RBC surface. While these proteins mediate interactions with host cells that contribute to disease pathogenesis, the infected RBC surface proteome remains poorly...
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2015
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| Online Access: | http://hdl.handle.net/1721.1/100270 https://orcid.org/0000-0001-7215-1439 https://orcid.org/0000-0002-6250-8796 |
| _version_ | 1826206882608447488 |
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| author | Birch, Christina M. Hou, Han Wei Han, Jongyoon Niles, Jacquin |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Birch, Christina M. Hou, Han Wei Han, Jongyoon Niles, Jacquin |
| author_sort | Birch, Christina M. |
| collection | MIT |
| description | Plasmodium falciparum malaria parasites invade and remodel human red blood cells (RBCs) by trafficking parasite-synthesized proteins to the RBC surface. While these proteins mediate interactions with host cells that contribute to disease pathogenesis, the infected RBC surface proteome remains poorly characterized. Here we use a novel strategy (I-SELEX) to discover high affinity aptamers that selectively recognize distinct epitopes uniquely present on parasite-infected RBCs. Based on inertial focusing in spiral microfluidic channels, I-SELEX enables stringent partitioning of cells (efficiency ≥ 10[superscript 6]) from unbound oligonucleotides at high volume throughput (~2 × 10[superscript 6] cells min[superscript −1]). Using an RBC model displaying a single, non-native antigen and live malaria parasite-infected RBCs as targets, we establish suitability of this strategy for de novo aptamer selections. We demonstrate recovery of a diverse set of aptamers that recognize distinct, surface-displayed epitopes on parasite-infected RBCs with nanomolar affinity, including an aptamer against the protein responsible for placental sequestration, var2CSA. These findings validate I-SELEX as a broadly applicable aptamer discovery platform that enables identification of new reagents for mapping the parasite-infected RBC surface proteome at higher molecular resolution to potentially contribute to malaria diagnostics, therapeutics and vaccine efforts. |
| first_indexed | 2024-09-23T13:39:44Z |
| format | Article |
| id | mit-1721.1/100270 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:39:44Z |
| publishDate | 2015 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1002702022-10-01T16:24:24Z Identification of malaria parasite-infected red blood cell surface aptamers by inertial microfluidic SELEX (I-SELEX) Birch, Christina M. Hou, Han Wei Han, Jongyoon Niles, Jacquin Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Birch, Christina M. Hou, Han Wei Han, Jongyoon Niles, Jacquin Plasmodium falciparum malaria parasites invade and remodel human red blood cells (RBCs) by trafficking parasite-synthesized proteins to the RBC surface. While these proteins mediate interactions with host cells that contribute to disease pathogenesis, the infected RBC surface proteome remains poorly characterized. Here we use a novel strategy (I-SELEX) to discover high affinity aptamers that selectively recognize distinct epitopes uniquely present on parasite-infected RBCs. Based on inertial focusing in spiral microfluidic channels, I-SELEX enables stringent partitioning of cells (efficiency ≥ 10[superscript 6]) from unbound oligonucleotides at high volume throughput (~2 × 10[superscript 6] cells min[superscript −1]). Using an RBC model displaying a single, non-native antigen and live malaria parasite-infected RBCs as targets, we establish suitability of this strategy for de novo aptamer selections. We demonstrate recovery of a diverse set of aptamers that recognize distinct, surface-displayed epitopes on parasite-infected RBCs with nanomolar affinity, including an aptamer against the protein responsible for placental sequestration, var2CSA. These findings validate I-SELEX as a broadly applicable aptamer discovery platform that enables identification of new reagents for mapping the parasite-infected RBC surface proteome at higher molecular resolution to potentially contribute to malaria diagnostics, therapeutics and vaccine efforts. National Institutes of Health (U.S.) (Director's New Innovator Award 1DP2OD007124) Singapore-MIT Alliance for Research and Technology. Infectious Disease Interdisciplinary Research Group Wade Fund MIT Startup Funds Singapore-MIT Alliance for Research and Technology. BioSystems and Micromechanics Interdisciplinary Research Group National Science Foundation (U.S.). Graduate Research Fellowship National Institutes of Health (U.S.) (Chemistry/Biology Interface Training Program Grant 1-T32-GM081081) 2015-12-15T18:06:35Z 2015-12-15T18:06:35Z 2015-07 2015-02 Article http://purl.org/eprint/type/JournalArticle 2045-2322 http://hdl.handle.net/1721.1/100270 Birch, Christina M., Han Wei Hou, Jongyoon Han, and Jacquin C. Niles. “Identification of Malaria Parasite-Infected Red Blood Cell Surface Aptamers by Inertial Microfluidic SELEX (I-SELEX).” Scientific Reports 5 (July 1, 2015): 11347. https://orcid.org/0000-0001-7215-1439 https://orcid.org/0000-0002-6250-8796 en_US http://dx.doi.org/10.1038/srep11347 Scientific Reports Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature |
| spellingShingle | Birch, Christina M. Hou, Han Wei Han, Jongyoon Niles, Jacquin Identification of malaria parasite-infected red blood cell surface aptamers by inertial microfluidic SELEX (I-SELEX) |
| title | Identification of malaria parasite-infected red blood cell surface aptamers by inertial microfluidic SELEX (I-SELEX) |
| title_full | Identification of malaria parasite-infected red blood cell surface aptamers by inertial microfluidic SELEX (I-SELEX) |
| title_fullStr | Identification of malaria parasite-infected red blood cell surface aptamers by inertial microfluidic SELEX (I-SELEX) |
| title_full_unstemmed | Identification of malaria parasite-infected red blood cell surface aptamers by inertial microfluidic SELEX (I-SELEX) |
| title_short | Identification of malaria parasite-infected red blood cell surface aptamers by inertial microfluidic SELEX (I-SELEX) |
| title_sort | identification of malaria parasite infected red blood cell surface aptamers by inertial microfluidic selex i selex |
| url | http://hdl.handle.net/1721.1/100270 https://orcid.org/0000-0001-7215-1439 https://orcid.org/0000-0002-6250-8796 |
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