NULISA: a novel proteomic liquid biopsy platform with attomolar sensitivity and high multiplexing

The blood proteome holds great promise for precision medicine but poses substantial challenges due to the low abundance of most plasma proteins and the vast dynamic range across the proteome. We report a novel proteomic technology - NUcleic acid Linked Immuno-Sandwich Assay (NULISA™) - that incorpor...

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Published inbioRxiv : the preprint server for biology
Main Authors Feng, Wei, Beer, Joanne, Hao, Qinyu, Ariyapala, Ishara S, Sahajan, Aparna, Komarov, Andrei, Cha, Katie, Moua, Mason, Qiu, Xiaolei, Xu, Xiaomei, Iyengar, Shweta, Yoshimura, Thu, Nagaraj, Rajini, Wang, Li, Yu, Ming, Engel, Kate, Zhen, Lucas, Xue, Wen, Lee, Chen-Jung, Park, Chan Ho, Peng, Cheng, Zhang, Kaiyuan, Grzybowski, Adrian, Hahm, Johnnie, Schmidt, Susanne V, Odainic, Alexandru, Spitzer, Jasper, Buddika, Kasun, Kuo, Dwight, Fang, Lei, Zhang, Bingqing, Chen, Steve, Latz, Eicke, Yin, Yiyuan, Luo, Yuling, Ma, Xiao-Jun
Format Journal Article
LanguageEnglish
Published United States 02.06.2023
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Abstract The blood proteome holds great promise for precision medicine but poses substantial challenges due to the low abundance of most plasma proteins and the vast dynamic range across the proteome. We report a novel proteomic technology - NUcleic acid Linked Immuno-Sandwich Assay (NULISA™) - that incorporates a dual capture and release mechanism to suppress the assay background and improves the sensitivity of the proximity ligation assay by over 10,000-fold to the attomolar level. It utilizes pairs of antibodies conjugated to DNA oligonucleotides that enable immunocomplex purification and generate reporter DNA containing target- and sample-specific barcodes for a next-generation sequencing-based, highly multiplexed readout. A 200-plex NULISA targeting 124 cytokines and chemokines and 80 other immune response-related proteins demonstrated superior sensitivity for detecting low-abundance proteins and high concordance with other immunoassays. The ultrahigh sensitivity allowed the detection of previously difficult-to-detect, but biologically important, low-abundance biomarkers in patients with autoimmune diseases and COVID-19. Fully automated NULISA addresses longstanding challenges in proteomic analysis of liquid biopsies and makes broad and in-depth proteomic analysis accessible to the general research community and future diagnostic applications.
AbstractList The blood proteome holds great promise for precision medicine but poses substantial challenges due to the low abundance of most plasma proteins and the vast dynamic range across the proteome. We report a novel proteomic technology - NUcleic acid Linked Immuno-Sandwich Assay (NULISA™) - that incorporates a dual capture and release mechanism to suppress the assay background and improves the sensitivity of the proximity ligation assay by over 10,000-fold to the attomolar level. It utilizes pairs of antibodies conjugated to DNA oligonucleotides that enable immunocomplex purification and generate reporter DNA containing target- and sample-specific barcodes for a next-generation sequencing-based, highly multiplexed readout. A 200-plex NULISA targeting 124 cytokines and chemokines and 80 other immune response-related proteins demonstrated superior sensitivity for detecting low-abundance proteins and high concordance with other immunoassays. The ultrahigh sensitivity allowed the detection of previously difficult-to-detect, but biologically important, low-abundance biomarkers in patients with autoimmune diseases and COVID-19. Fully automated NULISA addresses longstanding challenges in proteomic analysis of liquid biopsies and makes broad and in-depth proteomic analysis accessible to the general research community and future diagnostic applications.
Author Wang, Li
Beer, Joanne
Hahm, Johnnie
Zhang, Kaiyuan
Zhang, Bingqing
Moua, Mason
Yin, Yiyuan
Zhen, Lucas
Xue, Wen
Luo, Yuling
Sahajan, Aparna
Feng, Wei
Nagaraj, Rajini
Grzybowski, Adrian
Yu, Ming
Odainic, Alexandru
Fang, Lei
Komarov, Andrei
Park, Chan Ho
Hao, Qinyu
Lee, Chen-Jung
Buddika, Kasun
Iyengar, Shweta
Schmidt, Susanne V
Ariyapala, Ishara S
Ma, Xiao-Jun
Yoshimura, Thu
Engel, Kate
Xu, Xiaomei
Spitzer, Jasper
Kuo, Dwight
Peng, Cheng
Chen, Steve
Qiu, Xiaolei
Cha, Katie
Latz, Eicke
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