Simultaneous protein and RNA analysis in single extracellular vesicles, including viruses

The individual detection of human immunodeficiency virus (HIV) virions and resolution from extracellular vesicles (EVs) during analysis is a difficult challenge. Infectious enveloped virions and nonviral EVs are released simultaneously by HIV-infected host cells, in addition to hybrid viral EVs cont...

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Autor principal: Troyer, Zach (author)
Otros Autores: Gololobova, Olesia (author), Koppula, Aakash (author), Liao, Zhaohao (author), Horns, Felix (author), Elowitz, Michael B (author), Tosar Rovira, Juan Pablo (author), Batish, Mona (author), Witwer, Kenneth (author)
Formato: article
Lenguaje:inglés
Publicado: 2024
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Acceso en línea:https://hdl.handle.net/20.500.12008/50874
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author Troyer, Zach
author2 Gololobova, Olesia
Koppula, Aakash
Liao, Zhaohao
Horns, Felix
Elowitz, Michael B
Tosar Rovira, Juan Pablo
Batish, Mona
Witwer, Kenneth
author2_role author
author
author
author
author
author
author
author
author_browse Batish, Mona
Elowitz, Michael B
Gololobova, Olesia
Horns, Felix
Koppula, Aakash
Liao, Zhaohao
Tosar Rovira, Juan Pablo
Troyer, Zach
Witwer, Kenneth
author_facet Troyer, Zach
Gololobova, Olesia
Koppula, Aakash
Liao, Zhaohao
Horns, Felix
Elowitz, Michael B
Tosar Rovira, Juan Pablo
Batish, Mona
Witwer, Kenneth
author_role author
collection COLIBRI
dc.contributor.none.fl_str_mv Troyer Zach
Gololobova Olesia
Koppula Aakash
Liao Zhaohao
Horns Felix
Elowitz Michael B
Tosar Rovira Juan Pablo, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares.
Batish Mona
Witwer Kenneth
dc.creator.none.fl_str_mv Troyer, Zach
Gololobova, Olesia
Koppula, Aakash
Liao, Zhaohao
Horns, Felix
Elowitz, Michael B
Tosar Rovira, Juan Pablo
Batish, Mona
Witwer, Kenneth
dc.date.none.fl_str_mv 2024
2025-08-04T17:02:22Z
2025-08-04T17:02:22Z
dc.format.none.fl_str_mv 17 h
application/pdf
dc.identifier.none.fl_str_mv Troyer, Z, Gololobova, O, Koppula, A [y otros autores]. "Simultaneous protein and RNA analysis in single extracellular vesicles, including viruses". ACS Nano. [en línea] 2024, 18(39): 26568−26584. 17 h. DOI: 10.1021/acsnano.4c03679
1936-0851
https://hdl.handle.net/20.500.12008/50874
10.1021/acsnano.4c03679
dc.language.none.fl_str_mv en
eng
dc.publisher.none.fl_str_mv ACS Publications
dc.relation.none.fl_str_mv ACS Nano, 2024, 18(39): 26568−26584.
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
Licencia Creative Commons Atribución - No Comercial - Sin Derivadas (CC - By-NC-ND 4.0)
dc.source.none.fl_str_mv reponame:COLIBRI
instname:Universidad de la República
instacron:Universidad de la República
dc.subject.none.fl_str_mv Sngle-particle
Single-molecule
HIV
Extracellular vesicle
RNA
Protein
SP-IRIS
dc.title.none.fl_str_mv Simultaneous protein and RNA analysis in single extracellular vesicles, including viruses
dc.type.none.fl_str_mv Artículo
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
description The individual detection of human immunodeficiency virus (HIV) virions and resolution from extracellular vesicles (EVs) during analysis is a difficult challenge. Infectious enveloped virions and nonviral EVs are released simultaneously by HIV-infected host cells, in addition to hybrid viral EVs containing combinations of HIV and host components but lacking replicative ability. Complicating the issue, EVs and enveloped virions are both delimited by a lipid bilayer and share similar size and density. The feature that distinguishes infectious virions from host and hybrid EVs is the HIV genomic RNA (gRNA), which allows the virus to replicate. Singleparticle analysis techniques, which provide snapshots of single biological nanoparticles, could resolve infectious virions from EVs. However, current single-particle analysis techniques focus mainly on protein detection, which fail to resolve hybrid EVs from infectious virions. A method to simultaneously detect viral protein and internal gRNA in the same particle would allow resolution of infectious HIV from EVs and noninfectious virions. Here, we introduce SPIRFISH, a high-throughput method for single-particle protein and RNA analysis, combining single particle interferometric reflectance imaging sensor with singlemolecule fluorescence in situ hybridization. Using SPIRFISH, we detect HIV-1 envelope protein gp120 and genomic RNA within single infectious virions, allowing resolution against EV background and noninfectious virions. We further show that SPIRFISH can be used to detect specific RNAs within EVs. This may have major utility for EV therapeutics, which are increasingly focused on EV-mediated RNA delivery. SPIRFISH should enable single particle analysis of a broad class of RNAcontaining nanoparticles.
eu_rights_str_mv openAccess
format article
id anni_8a2e4ee826ba8ba0e4820ce4c778df0d
identifier_str_mv Troyer, Z, Gololobova, O, Koppula, A [y otros autores]. "Simultaneous protein and RNA analysis in single extracellular vesicles, including viruses". ACS Nano. [en línea] 2024, 18(39): 26568−26584. 17 h. DOI: 10.1021/acsnano.4c03679
1936-0851
10.1021/acsnano.4c03679
instacron_str Universidad de la República
institution Universidad de la República
instname_str Universidad de la República
language eng
language_invalid_str_mv en
network_acronym_str anni
network_name_str oai-lr-anni
oai_identifier_str oai:colibri.udelar.edu.uy:20.500.12008/50874
publishDate 2024
publishDateSort 2024
publisher.none.fl_str_mv ACS Publications
reponame_str COLIBRI
repository.mail.fl_str_mv
repository.name.fl_str_mv
repository_id_str
rights_invalid_str_mv Licencia Creative Commons Atribución - No Comercial - Sin Derivadas (CC - By-NC-ND 4.0)
spelling Simultaneous protein and RNA analysis in single extracellular vesicles, including virusesTroyer, ZachGololobova, OlesiaKoppula, AakashLiao, ZhaohaoHorns, FelixElowitz, Michael BTosar Rovira, Juan PabloBatish, MonaWitwer, KennethSngle-particleSingle-moleculeHIVExtracellular vesicleRNAProteinSP-IRISThe individual detection of human immunodeficiency virus (HIV) virions and resolution from extracellular vesicles (EVs) during analysis is a difficult challenge. Infectious enveloped virions and nonviral EVs are released simultaneously by HIV-infected host cells, in addition to hybrid viral EVs containing combinations of HIV and host components but lacking replicative ability. Complicating the issue, EVs and enveloped virions are both delimited by a lipid bilayer and share similar size and density. The feature that distinguishes infectious virions from host and hybrid EVs is the HIV genomic RNA (gRNA), which allows the virus to replicate. Singleparticle analysis techniques, which provide snapshots of single biological nanoparticles, could resolve infectious virions from EVs. However, current single-particle analysis techniques focus mainly on protein detection, which fail to resolve hybrid EVs from infectious virions. A method to simultaneously detect viral protein and internal gRNA in the same particle would allow resolution of infectious HIV from EVs and noninfectious virions. Here, we introduce SPIRFISH, a high-throughput method for single-particle protein and RNA analysis, combining single particle interferometric reflectance imaging sensor with singlemolecule fluorescence in situ hybridization. Using SPIRFISH, we detect HIV-1 envelope protein gp120 and genomic RNA within single infectious virions, allowing resolution against EV background and noninfectious virions. We further show that SPIRFISH can be used to detect specific RNAs within EVs. This may have major utility for EV therapeutics, which are increasingly focused on EV-mediated RNA delivery. SPIRFISH should enable single particle analysis of a broad class of RNAcontaining nanoparticles.ACS PublicationsTroyer ZachGololobova OlesiaKoppula AakashLiao ZhaohaoHorns FelixElowitz Michael BTosar Rovira Juan Pablo, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares.Batish MonaWitwer Kenneth2025-08-04T17:02:22Z2025-08-04T17:02:22Z2024Artículoinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion17 happlication/pdfTroyer, Z, Gololobova, O, Koppula, A [y otros autores]. "Simultaneous protein and RNA analysis in single extracellular vesicles, including viruses". ACS Nano. [en línea] 2024, 18(39): 26568−26584. 17 h. DOI: 10.1021/acsnano.4c036791936-0851https://hdl.handle.net/20.500.12008/5087410.1021/acsnano.4c03679reponame:COLIBRIinstname:Universidad de la Repúblicainstacron:Universidad de la RepúblicaenengACS Nano, 2024, 18(39): 26568−26584.Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad de la República.(Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. Nº 16 de C.D.C. de 07/10/2014)info:eu-repo/semantics/openAccessLicencia Creative Commons Atribución - No Comercial - Sin Derivadas (CC - By-NC-ND 4.0)oai:colibri.udelar.edu.uy:20.500.12008/508742026-04-14T10:10:53Z
spellingShingle Simultaneous protein and RNA analysis in single extracellular vesicles, including viruses
Troyer, Zach
Sngle-particle
Single-molecule
HIV
Extracellular vesicle
RNA
Protein
SP-IRIS
status_str publishedVersion
title Simultaneous protein and RNA analysis in single extracellular vesicles, including viruses
title_full Simultaneous protein and RNA analysis in single extracellular vesicles, including viruses
title_fullStr Simultaneous protein and RNA analysis in single extracellular vesicles, including viruses
title_full_unstemmed Simultaneous protein and RNA analysis in single extracellular vesicles, including viruses
title_short Simultaneous protein and RNA analysis in single extracellular vesicles, including viruses
title_sort Simultaneous protein and RNA analysis in single extracellular vesicles, including viruses
topic Sngle-particle
Single-molecule
HIV
Extracellular vesicle
RNA
Protein
SP-IRIS
url https://hdl.handle.net/20.500.12008/50874