HIV Apheresis Tags (HIVAT) Aided Elimination of Viremia.

Molecular and cellular therapies Pub Date : 2018-01-01 Epub Date: 2018-06-21
Marek Malecki, Bianka Saetre
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引用次数: 0

Abstract

Introduction: HIV viremia is the essential element for progression of an initial HIV infection into AIDS and death. The currently approved management relies primarily on chemotherapy repressing the HIV replication in the infected CD4+ cells, although with severe systemic adverse effects. The problem is that it does not physically eliminate viruses, which then not only keep infecting healthy cells of these patients, but also promote infections of other people.

Specific aim: An overall objective of our work is biomolecular engineering of virus apheresis tags (VAT) that eliminate viremias without adverse effects. The specific aim of this project was biomolecular engineering of Human Immunodeficiency Virus Apheresis Tags (HIVAT): CD4-Au-Fe3O4, CD4-SiO2-Fe3O4, anti-gp120-Au-Fe3O4, and anti-gp120-SiO2-Fe3O4.

Healthy donors and patients: Per the Institutional Review Board's approval and in compliance with Declaration of Helsinki, healthy donors and patients were presented with Patient Bill of Rights and provided Patient Informed Consent, while all the procedures were pursued by the licensed physicians.

Materials and methods: CD4, gp120, gp41, gp160, anti-gp120, p24 were transgenomically expressed. Superparamagnetic core-shell particles (SPM-CSP) were synthesized. SPM-CSP were used as the nucleation centers for assembling the expressed molecules upon them to create virus apheresis tags (VAT). VAT were injected into the blood or lymph acquired from the HIV+ and HBV+ patients followed by apheresis at 0.47 - 9.4 T. VAT efficacy in eliminating viremia was determined through immunoblots, NMR and q-RT-PCR.

Results: Treatment of blood or lymph of the HIV+ patients' with VAT followed by virus apheresis resulted in rapid elimination of the HIV viremia. Efficacy of apheresis was contingent upon the gravity of viremia versus doses and regimens of VAT. Importantly, administration of VAT also effectively improved levels of non-infected CD4+ lymphocytes.

Discussion / conclusions: Herein, we present the proof of concept for a new, effective treatment with virus apheresis tags (VAT), specifically Human Immunodeficiency Virus Apheresis Tags (HIVAT), of the HIV+ patients' blood and lymph, which is eliminating the HIV viremia.It can be easily adapted as treatments of viremias perpetrated by other deadly viruses, which we vigorously pursue.

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HIV单采标签(HIVAT)辅助消除病毒血症。
引言:艾滋病病毒血症是最初感染艾滋病发展为艾滋病并导致死亡的重要因素。目前批准的治疗方法主要依靠化疗来抑制感染的CD4+细胞中的HIV复制,尽管会产生严重的全身不良反应。问题是,它并不能从物理上消除病毒,病毒不仅会继续感染这些患者的健康细胞,还会促进其他人的感染。具体目标:我们工作的总体目标是对病毒单采标签(VAT)进行生物分子工程,以消除病毒血症而不会产生不良影响。该项目的具体目标是人类免疫缺陷病毒单采标签(HIVAT)的生物分子工程:CD4-Au-Fe3O4、CD4-SiO2-Fe3O4、抗gp120-Au-Fe3 O4和抗gp120-SiO2-Fe3 O4。健康的捐赠者和患者:根据机构审查委员会的批准并符合赫尔辛基宣言,健康捐赠者和患者收到了《患者权利法案》,并获得了患者知情同意书,而所有程序都由持照医生执行。材料和方法:CD4、gp120、gp41、gp160、抗gp120、p24转基因表达。合成了超顺磁性核壳粒子(SPM-CSP)。SPM-CSP用作成核中心,用于将表达的分子组装在其上以产生病毒单采标签(VAT)。通过免疫印迹、核磁共振和q-RT-PCR测定了从HIV+和HBV+患者获得的血液或淋巴中注射增值税,然后在0.47-9.4T时单采。结果:用增值税治疗HIV+患者的血液或淋巴液,然后单采病毒,可以快速消除HIV病毒血症。单采的疗效取决于病毒血症的严重程度与增值税的剂量和方案。重要的是,施用增值税还有效地提高了未感染的CD4+淋巴细胞的水平。讨论/结论:在此,我们提出了一种新的、有效的治疗HIV+患者血液和淋巴的病毒单采标记物(VAT),特别是人类免疫缺陷病毒单采标签物(HIVAT)的概念证明,它可以消除HIV病毒血症。它可以很容易地适应其他致命病毒引起的病毒血症的治疗,这是我们大力追求的。
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