Broken String Biosciences launched an

Broken String Biosciences推出了一款

early access program

早期访问计划

(EAP) through which select developers of gene edited therapeutics will be able to use Broken String’s INDUCE-seq

(EAP) 通过该计划，选定的基因编辑治疗药物开发者将能够使用 Broken String 的 INDUCE-seq。

®

``` ® ``` 没有可翻译的内容，®是一个注册商标符号。

technology in their own labs for detecting and quantifying both the on- and off-target double strand DNA breaks that occur as a result of CRISPR and other nuclease-based gene editing in cells.

在他们自己的实验室中用于检测和定量CRISPR和其他基于核酸酶的基因编辑在细胞中产生的脱靶双链DNA断裂的技术。

Building on the success of Broken String’s service-based INDUCE-seq lab offering, the new Catalyst program will support integration of the platform into participants’ therapeutics development pipelines at the earliest discovery and optimization stages.

基于Broken String的服务型INDUCE-seq实验室的成功，新的Catalyst项目将支持该平台在参与者药物开发流程的最早发现和优化阶段进行整合。

Users will be able to use INDUCE-seq on site to derive precise, real-time identification of exactly where DNA breaks occur, in parallel with the process of iterating on guide RNA designs and optimize delivery systems, and in diverse cell and tissue types.

用户将能够现场使用INDUCE-seq，以实现DNA断裂精确、实时的识别，同时进行引导RNA设计的迭代优化和递送系统的优化，并适用于多种细胞和组织类型。

The Broken String Biosciences team. [Broken String Biosciences]

破弦生物科技团队。[破弦生物科技]

The University of Cardiff spin-out Broken String aims to establish INDUCE-seq as the gold standard technology for precisely mapping gene editing-related double strand DNA breaks in cells, to ensure gene editing safety. “Our technology is applicable to pretty much every stage of the gene edited therapeutic pipeline development, right from early discovery, where you are screening high numbers of nucleases and guides and different delivery technologies,” said Felix Dobbs, PhD, Broken String co-founder and CEO, to .

卡迪夫大学衍生公司Broken String旨在将INDUCE-seq确立为细胞中基因编辑相关双链DNA断裂精确定位的黄金标准技术，以确保基因编辑的安全性。“我们的技术几乎适用于基因编辑治疗开发流程的每一个阶段，从早期发现开始，那时你需要筛选大量的核酸酶、引导序列和不同的递送技术，”Broken String联合创始人兼首席执行官Felix Dobbs博士说。

GEN

``` 通用 ```

.

请提供需要翻译的文本。

“The platform enables direct, unbiased genome-wide identification and quantification of the exact position of double strand DNA breaks in edited cells, in clinically relevant samples, to support progression through discovery and preclinical development, and IND application.” Dobbs maintains the EAP will enable broader industry-wide adoption of INDUCE-seq and position the technology as an essential safety component supporting the development of the next generation of gene-edited therapeutics..

“该平台能够在临床相关的样本中，对编辑细胞中的双链DNA断裂的确切位置进行直接、无偏的全基因组识别和定量，以支持从发现到临床前开发以及IND申请的过程。”Dobbs认为EAP将促进INDUCE-seq在全行业的更广泛采用，并将这项技术定位为支持下一代基因编辑治疗药物开发的重要安全组件。

Credit: Broken String Biosciences

``` 来源：Broken String Biosciences ```

In contrast with current platforms, INDUCE-seq is precise and sensitive, PCR free, and cell and nuclease-agnostic. The technology has been developed to solve what the company describes as a fundamental gene editing safety challenge, in that developers need the ability to accurately and reproducibly assess both on- and off-target double strand DNA breaks, genome wide, and at high resolution.

与现有平台相比，INDUCE-seq精确灵敏，无需PCR，且不受细胞和核酸酶限制。该技术旨在解决公司所描述的基本基因编辑安全挑战，即开发者需要能够准确且可重复地评估全基因组范围内的脱靶双链DNA断裂，并以高分辨率进行。

The ability to identify and map double strand breaks resulting from a gene edit reproducibly and cost effectively will be crucial for ensuring the efficacy and safety of relevant therapeutics as they progress through development to market, Dobbs commented to .

Dobbs评论说，能够可靠且经济地识别和绘制因基因编辑产生的双链断裂，对于确保相关疗法的有效性和安全性至关重要，这些疗法在开发过程中将逐步进入市场。

GEN

``` 通用 ```

.

请提供需要翻译的文本。

“There is an imperative to satisfy regulatory scrutiny surrounding CAR-T cell and other gene-edited therapies. Historically companies in this space may have simply predicted where these breaks may occur and monitor them in patients, but to achieve regulatory clearance developers must be able to determine empirically where these sites are.”.

“有必要满足对CAR-T细胞和其他基因编辑疗法的监管审查。历史上，该领域的公司可能只是预测这些断裂可能发生的位置并监测患者中的这些位置，但为了获得监管批准，开发者必须能够实证地确定这些位置。”。

Industry has until now lacked a gold standard for detecting on- and off-target edits, Dobbs noted. “Currently there are a handful of technologies, which might be described as “home-brewed” adaptations of methods and protocols published in the literature, but until now there hasn’t really been one standardized technology.” And existing approaches may also present challenges, including PCR-induced bias, and missed rare, low-frequency unintended edits that may be dangerous and could have “disastrous consequences” for clinical programs, he pointed out.

多布斯指出，迄今为止，工业界在检测脱靶编辑方面缺乏一个黄金标准。“目前有几种技术，可以被描述为文献中发表的方法和协议的‘自制’改编版，但到目前为止还没有一个标准化的技术。”他指出，现有的方法也可能带来挑战，包括PCR引起的偏差，以及可能危险的罕见低频非目标编辑，这些编辑可能会对临床项目产生“灾难性后果”。

“And rare double stranded breaks may not be detected by existing whole genome sequencing approaches.”.

“现有的全基因组测序方法可能无法检测到罕见的双链断裂。”。

Over recent years companies have had access to INDUCE-seq technology via services offered by Broken String at its labs in Cambridge, U.K. Through the Catalyst program, partners will be equipped to set up and run the INDUCE-seq platform within their own labs, giving them the ability to generate results in just days.

近年来，公司可以通过位于英国剑桥的Broken String实验室提供的服务访问INDUCE-seq技术。通过催化剂计划，合作伙伴将能够在其自己的实验室中建立和运行INDUCE-seq平台，从而使他们能够在短短几天内生成结果。

INDUCE-seq should be within the reach of most conventional lab setups, using standard liquid handling equipment, Dobbs stated..

多布斯表示，INDUCE-seq应该在大多数常规实验室设置的可及范围内，使用标准的液体处理设备即可。

Participants can then easily conduct repeated assessments as they refine and validate editing strategies, harnessing INDUCE-seq to rapidly identify unintended DNA breaks that might compromise the safety or efficacy of therapies. For instance, therapies targeting rare liver diseases or neurological conditions can be tested for unintended effects on nearby tissues, an increasingly important requirement for regulatory approval.

参与者可以轻松地进行重复评估，以完善和验证编辑策略，并利用INDUCE-seq快速识别可能影响疗法安全性和有效性的小型DNA断裂。例如，针对罕见肝脏疾病或神经系统疾病的疗法可以测试其对周围组织的意外影响，这是监管批准越来越重要的要求。

This capability will be especially valuable as gene editing expands to treat complex, multi-gene disorders, where multiple targets and delivery mechanisms must be carefully balanced to minimize risks, the company believes..

该公司认为，随着基因编辑扩展到治疗复杂的多基因疾病，这一能力将变得尤为重要，在这些疾病中，必须仔细平衡多个目标和传递机制以最大限度地降低风险。

In-house application of INDUCE-seq will help to springboard organizations’ ability to negotiate regulatory approval when progressing from preclinical to clinical development, ultimately supporting commercialization of gene-edited therapeutics, Dobbs stressed. The gene editing industry has reached an inflection point, where the momentum required to reach its potential can only be sustained by expanding patient access—which requires standardization, faster drug development, and robust safety characterization, he believes..

多布斯强调，在内部应用INDUCE-seq将有助于组织在从临床前阶段过渡到临床开发阶段时谈判监管批准的能力，最终支持基因编辑治疗的商业化。他认为，基因编辑行业已经达到了一个拐点，要发挥其潜力，只能通过扩大患者准入来维持这种势头，而这需要标准化、更快的药物开发和健全的安全性表征。

Felix Dobbs, PhD, co-founder and CEO

``` 费利克斯·多布斯博士，联合创始人兼首席执行官 ```

Broken String Biosciences

断弦生物科技公司

“One of the real challenges faced by the field and one of the things that we are trying to address is that there is no safety standard, and this creates a real uncertainty for companies,” Dobbs explained. “There is a lack of standardization for existing technologies, and organizations are guessing what the FDA will require or accept.”.

“该领域面临的一个真正挑战，也是我们试图解决的问题之一，是没有安全标准，这给公司造成了真正的不确定性，”Dobbs解释说。“现有技术缺乏标准化，组织在猜测FDA会要求或接受什么。”。

In contrast with such technologies, INDUCE-seq is both a reproducible and highly precise genome-wide measurement platform for mapping all the break points that can occur in cells naturally as well as through the gene editing process, Dobbs further explained to

与这些技术相比，INDUCE-seq是一种可重复且高度精确的全基因组测量平台，可用于绘制细胞中自然发生以及通过基因编辑过程发生的すべてのブレークポイントをマッピングするためのDobbsはさらに説明した。

GEN

``` 通用 ```

. “We’ve brought different elements together to address the challenges faced by other technologies that are very slow and laborious. We have developed a novel way of labeling DNA breaks in cells, and then reading them out by sequencing. Using our novel, PCR-free methodology we get a very precise record of those breakpoints and their frequencies in a way that’s relatively easy to do and scalable.

“我们汇集了不同的元素来解决其他技术面临的缓慢且繁琐的挑战。我们开发了一种在细胞中对DNA断裂进行标记的新方法，并通过测序读取它们。使用我们的新型、无PCR的方法，我们可以精确记录这些断点及其频率，这种方法相对容易操作且可扩展。”

Core to how the technology works is our novel way of preparing the libraries for sequencing, and it’s this that gives us this very clean readout, free of PCR. It’s a process-, not equipment-based platform. Through the Catalyst program we will help with set up, and how to feed data into our cloud-based informatics platform.”.

技术工作的核心在于我们准备测序文库的创新方法，这使我们能够获得没有PCR污染的非常清晰的读取结果。这是一个基于过程而非设备的平台。通过催化计划，我们将帮助设置，并指导如何将数据输入到我们的基于云的信息分析平台。

Broken String raised a $15 million Series A round of financing in September 2023, which supported the development of its “platform as a service” offering. The exact format of the new Catalyst program is still evolving, Dobbs suggested to

Broken String在2023年9月筹集了1500万美元的A轮融资，这支持了其“平台即服务”产品的开发。Dobbs建议，新的催化剂计划的具体形式仍在不断发展。

GEN

``` 通用 ```

, “but the idea is that we will support participants’ implementation of all the lab components and provide access to the cloud-based informatics platform.”

“但我们的想法是支持参与者实施所有实验室组件，并提供对基于云的信息平台的访问。”

In parallel, Broken String is continuing to evolve its core INDUCE-seq platform. “We aim to adapt as new CRISPR systems are developed,” Dobbs said. “Our technology can also be modified to detect editing from different editing systems, such as base editing. It’s a rapidly evolving field, and we want to be part of the story, in bringing this whole generation of medicines to patients.”.

与此同时，Broken String公司正在继续发展其核心的INDUCE-seq平台。“我们希望随着新的CRISPR系统的开发进行适应，”Dobbs说。“我们的技术还可以被修改以检测不同编辑系统（如碱基编辑）的编辑。这是一个快速发展的领域，我们希望成为其中的一部分，将这一整代药物带给患者。”。

Aside from leveraging use of INDUCE-seq in the development of gene edited therapeutics, Broken String is also working with academia to apply INDUCE-seq in the field of disease research. In 2024 the company set up a

除了利用INDUCE-seq在基因编辑治疗药物开发中的应用外，Broken String还在与学术界合作，将INDUCE-seq应用于疾病研究领域。2024年，该公司设立了一个

partnership with the Francis Crick Institute

与弗朗西斯·克里克研究所的合作

, through which INDUCE-seq will be harnessed to investigate the impact of genomic instability on the development of amyotrophic lateral sclerosis.

，通过该方法将利用INDUCE-seq研究基因组不稳定对肌萎缩侧索硬化症发展的影响。

News

``` 新闻 ```

Amyotrophic lateral sclerosis

肌萎缩侧索硬化症

Gene editing

基因编辑

Whole-genome sequencing

全基因组测序

Broken String Biosciences

破损字符串生物科学公司

INDUCE-seq

INDUCE-seq ``` 翻译成中文为： ``` 诱导测序 ```