DURHAM, N.C. & SEATTLE--(BUSINESS WIRE)--Leading epigenome editing company Tune Therapeutics presented data in support of its chronic Hepatitis B Virus (HBV) program, demonstrating the ability to durably silence essential mechanisms of viral replication and persistence across a range of model systems..

北卡罗来纳州达勒姆和西雅图——（商业新闻短讯）——领先的表观基因组编辑公司Tune Therapeutics提供了支持其慢性乙型肝炎病毒（HBV）计划的数据，证明了在一系列模型系统中持久沉默病毒复制和持续存在的基本机制的能力。。

TUNE-401 represents a fundamentally new approach to HBV treatment, in that it utilizes Tune’s precision genetic tuning platform, TEMPO, to inactivate viral DNA integrated into host chromosomes, while simultaneously silencing the extra-chromosomal, cccDNA “viral factories” necessary for sustained HBV infection.

TUNE-401代表了一种全新的HBV治疗方法，它利用TUNE的精确基因调节平台TEMPO来灭活整合到宿主染色体中的病毒DNA，同时沉默持续HBV感染所必需的额外染色体cccDNA“病毒工厂”。

Importantly, the TEMPO platform does this via epigenetic processes, and without cutting, damaging, or altering genomic DNA sequences in any way..

重要的是，TEMPO平台通过表观遗传过程做到这一点，并且不会以任何方式切割，破坏或改变基因组DNA序列。。

The ability to suppress the virus in both contexts – both within and outside the host genome – is an established prerequisite for control of the virus in chronic HBV patients, and this new epigenetic silencing approach offers a pathway toward a functional cure for HBV as a standalone therapy.

在宿主基因组内外的两种情况下抑制病毒的能力是控制慢性HBV患者病毒的既定先决条件，这种新的表观遗传沉默方法为HBV的功能性治愈提供了一条途径，作为一种独立的治疗方法。

The Tune HBV data, shared for the first time at the 2023 HepDART hepatology conference, showed:

在2023年HepDART肝病学会议上首次分享的Tune HBV数据显示：

near-complete repression of viral DNA in primary human hepatocytes and cell lines in vitro, with ongoing durability now beyond 550 days, and more than 275 cell doublings

在体外对原代人肝细胞和细胞系中的病毒DNA进行近乎完全的抑制，目前持续的持久性超过550天，细胞倍增超过275倍

similarly high levels of repression in successfully epi-edited cells in vivo, using chimeric, true-infection mouse models

使用嵌合的真实感染小鼠模型，在体内成功编辑epi的细胞中也有类似的高水平抑制

highly specific targeting and methylation by TUNE-401 for both integrated virus and cccDNA – with little or no expression change in non-targeted genes

TUNE-401对整合病毒和cccDNA的高度特异性靶向和甲基化-非靶向基因的表达变化很小或没有变化

Moreover, these results were achieved via a single target sequence, common to all viral contexts and locations within the cell, and highly conserved across HBV genotypes.

此外，这些结果是通过单个靶序列实现的，该序列是细胞内所有病毒背景和位置共有的，并且在HBV基因型中高度保守。

“We used TEMPO to screen for epigenetic repression targets that are active in cccDNA, and also in integrated HBV DNA,” explained Principal Scientist Brian Cosgrove, who presented the data at HepDART. “Through the richness of these data sets, we found multiple repression candidates that worked well in both contexts.

首席科学家布莱恩·科斯格罗夫（BrianCosgrove）解释说：“我们使用TEMPO来筛选在cccDNA和整合的HBV DNA中有活性的表观遗传抑制靶标”，他在HepDART上提供了这些数据。“通过这些数据集的丰富性，我们发现了在这两种情况下都有效的多种压制候选人。

The most compelling targets went on to yield near-complete repression of viral DNA in primary human hepatocytes, when corrected for per-cell delivery efficiency limits.”.

当校正每细胞递送效率限制时，最引人注目的靶标继续产生对原代人肝细胞中病毒DNA的近乎完全抑制。”。

In validating this target in vivo, Tune took care to select a comprehensive and informative HBV infection model featuring humanized FRG mice.

在体内验证这一目标时，Tune注意选择了一种以人源化FRG小鼠为特征的全面且信息丰富的HBV感染模型。

“We know from clinical research,” said Cosgrove, “that less than 5 percent of chronic HBV patients achieve full viral clearance and cure. Many who do, however, show epigenetic inactivation of the cccDNA. And while a variety of in vivo models exist for HBV infection, very few allow for the effective study of HBV regulation in its natural, extrachromosomal (cccDNA) context.

Cosgrove说：“我们从临床研究中知道，不到5%的慢性HBV患者能够完全清除病毒并治愈。然而，许多人确实表现出cccDNA的表观遗传失活。尽管存在多种HBV感染的体内模型，但很少有人能够在其天然的染色体外（cccDNA）环境中有效研究HBV的调节。

The chimeric FRG mouse model does just that.”.

嵌合FRG小鼠模型就是这样做的。”。

Chimeric FRG mice are created via the ablation and replacement of mouse liver cells with transplanted, human hepatocytes – effectively “humanizing” the liver. As such, they represent the gold standard for assessing the dose and efficacy for liver-directed therapeutics ahead of human clinical trials.

嵌合FRG小鼠是通过用移植的人肝细胞消融和替代小鼠肝细胞而产生的，有效地“人源化”了肝脏。因此，它们代表了在人类临床试验之前评估肝脏导向疗法剂量和疗效的金标准。

When tested in this model system, TUNE-401 showed high repression in delivered cells..

当在该模型系统中进行测试时，TUNE-401在递送的细胞中显示出高度抑制。。

Though no large animal model is available for HBV, Tune has demonstrated durable, liver-directed epi-editing of non-human primates (NHPs) using a surrogate target (PCSK9) and the same, essential mode of action – targeted DNA methylation.

尽管没有针对HBV的大型动物模型，但Tune已经证明使用替代靶标（PCSK9）和相同的基本作用模式靶向DNA甲基化对非人灵长类动物（NHP）进行了持久的，肝脏定向的epi编辑。

“Based on the breadth of our preclinical data, we have every reason to believe that this novel therapeutic strategy will translate,” says Derek Jantz, Chief Scientific Officer at Tune Therapeutics. “We sincerely hope that this will revitalize the field and lead to the standalone functional cure that HBV patients have been waiting for.”.

Tune Therapeutics首席科学官德里克·扬茨（DerekJantz）表示：“基于我们临床前数据的广度，我们有充分的理由相信这种新型治疗策略将得到转化。”。“我们衷心希望这将振兴该领域，并导致HBV患者一直在等待的独立功能性治疗。”。

Tune expects its HBV program to enter the clinic by the end of 2024, under the guidance of leading international clinical investigator Dr. Edward Gane.

Tune预计，在领先的国际临床研究者爱德华·甘恩博士的指导下，其HBV项目将于2024年底进入诊所。

About Tune Therapeutics

关于Tune Therapeutics

Armed with its powerful and innovative genetic tuning platform (TEMPO), Tune Therapeutics aims to bring gene, cell, and regenerative therapies into a new era of human medicine – expanding their range of application to common, chronic and age-related diseases that are straining healthcare systems and limiting human healthspan on a global scale..

凭借其强大而创新的基因调节平台（TEMPO），Tune Therapeutics旨在将基因，细胞和再生疗法带入人类医学的新时代-将其应用范围扩展到常见，慢性和与年龄相关的疾病，这些疾病正在使医疗保健系统紧张，并在全球范围内限制人类健康。。

Tune is currently hiring for additional members to join the team. For more information, please visit https://tunetx.com/join-the-band/.

Tune目前正在招募其他成员加入团队。有关更多信息，请访问https://tunetx.com/join-the-band/.

About TUNE-401

关于TUNE-401

TUNE-401 is a first-in-class investigational product candidate for the treatment of Hepatitis B (HBV) infection. TUNE-401 utilizes Tune’s TEMPO platform to epigenetically silence viral HBV DNA in host chromosomes, while simultaneously silencing the extra-chromosomal, cccDNA “viral factories” necessary for sustained HBV infection.

TUNE-401是治疗乙型肝炎（HBV）感染的一流候选研究产品。TUNE-401利用TUNE的TEMPO平台表观遗传沉默宿主染色体中的病毒HBV DNA，同时沉默持续HBV感染所必需的额外染色体cccDNA“病毒工厂”。

Lipid nanoparticle technology for TUNE-401 has been provided by Acuitas Therapeutics Inc..

用于TUNE-401的脂质纳米颗粒技术由Acuitas Therapeutics Inc.提供。。