開發一種靈敏的多檢測平台，用於監測慢性乙型肝炎病毒感

StephenW

開發一種靈敏的多檢測平台，用於監測慢性乙型肝炎病毒感染患者的低水平 HBV DNA 和 pgRNA
冉顏 1 ，蔡大偉 2 ，Lea Ouyang 2 ，Richard Colonno 2 ，Qi Huang 2 ，Kathryn M Kitrinos 2
隸屬關係
隸屬關係

    1
    Assembly Biosciences，南舊金山，加利福尼亞州，美國。電子地址：[email protected]。
    2
    Assembly Biosciences，南舊金山，加利福尼亞州，美國。

    PMID：36332714 DOI：10.1016/j.jviromet.2022.114640

抽象的

儘管延長了核苷（酸）化物 (NrtI) 治療，但 HBV 治愈率仍然很低，這可能是由於持續的殘留病毒複製和無法消除共價閉合環狀 DNA (cccDNA)。正在探索具有新的抗乙型肝炎病毒 (HBV) 作用機制的療法，目標是實現持續的非治療反應和功能性治愈，而無需終生治療。最近的研究表明，血清 HBV DNA 水平（病毒複製的生物標誌物）與血清前基因組 RNA (pgRNA) 水平（肝內 cccDNA 轉錄活性的替代指標）相結合，可以更好地預測肝臟相關並發症的風險。目前的 HBV DNA 檢測，如 COBAS AmpliPrep/COBAS TaqMan HBV 檢測 v2.0，可將 HBV DNA 定量至 20 IU/mL，但無法監測接受 NrtI 治療的患者體內殘留病毒的損失。目前尚無經批准可用於檢測血清/血漿 HBV pgRNA 水平的商業化檢測方法。我們開發了一個高靈敏度核酸檢測的多檢測組，旨在監測臨床標本中 HBV DNA、pgRNA 和總核酸（TNA、複合 DNA+pgRNA）的水平，並監測新抗病毒聯合方案治療期間的變化。

關鍵詞：DNA；乙肝病毒； pgRNA；總核酸。

版權所有 © 2022。Elsevier B.V. 出版
利益衝突聲明

競爭利益聲明 作者聲明以下可能被視為潛在競爭利益的經濟利益/個人關係： Ran Yan 和 Kathryn M. Kitrinos 是 Assembly Biosciences 的員工和股東。蔡大偉、Lea Ouyang、Richard Colonno 和 Qi Huang 在研究期間是 Assembly Biosciences 的員工和股東。

StephenW

Development of a sensitive, multi-assay platform to monitor low levels of HBV DNA and pgRNA in patients with chronic Hepatitis B virus infection
Ran Yan  1 , Dawei Cai  2 , Lea Ouyang  2 , Richard Colonno  2 , Qi Huang  2 , Kathryn M Kitrinos  2
Affiliations
Affiliations

    1
    Assembly Biosciences, South San Francisco, CA, USA. Electronic address: [email protected].
    2
    Assembly Biosciences, South San Francisco, CA, USA.

    PMID: 36332714 DOI: 10.1016/j.jviromet.2022.114640

Abstract

HBV cure rates remain low despite prolonged nucleos(t)ide (NrtI) therapy, likely due to persistent residual viral replication and an inability to eliminate covalently closed circular DNA (cccDNA). Therapies with novel mechanisms of action against hepatitis B virus (HBV) are being explored with the goal of achieving sustained off-treatment response and a functional cure without requiring lifelong therapy. Recent studies have indicated that serum HBV DNA levels (a biomarker for viral replication) combined with serum pregenomic RNA (pgRNA) levels (a surrogate for intrahepatic cccDNA transcriptional activity), may provide a better prediction for the risk of liver-related complications. Current HBV DNA assays, such as the COBAS AmpliPrep/COBAS TaqMan HBV test v2.0, quantitate HBV DNA down to 20 IU/mL, but are not able to monitor loss of residual virus in patients on NrtI therapy. There are no commercially available assays approved to detect serum/plasma HBV pgRNA levels. We have developed a multi-assay panel of highly sensitive nucleic acid assays designed to monitor levels of HBV DNA, pgRNA and total nucleic acids (TNA, composite DNA+pgRNA) in clinical specimens and to monitor changes during treatment with new antiviral combination regimens.

Keywords: DNA; HBV; pgRNA; total nucleic acid.

Copyright © 2022. Published by Elsevier B.V.
Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ran Yan and Kathryn M. Kitrinos are employees and shareholders of Assembly Biosciences. Dawei Cai, Lea Ouyang, Richard Colonno, and Qi Huang were employees and shareholders of Assembly Biosciences during the study.