Click here to close now.


News Feed Item

First-In-Man Study Of Genome Editing Using Sangamo's ZFN Technology Published In New England Journal Of Medicine

Treatment with Sangamo's ZFN- Modified T-cells (SB-728-T) Provides Functional Control of HIV without Antiretroviral Drugs

RICHMOND, Calif., March 5, 2014 /PRNewswire/ -- Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced today the publication in the New England Journal of Medicine of the first clinical study of its proprietary zinc finger nuclease (ZFN)-based genome editing technology in humans. Data from the study, carried out in HIV-positive subjects, demonstrate that the T-cell genome can be safely engineered to mimic a naturally occurring mutation that provides resistance to HIV infection. ZFN-modified T-cells are well tolerated when reinfused and treatment is associated with decreased viral loads (VLs) in several subjects who were taken off their antiretroviral therapy (ART) including one whose viral load became undetectable. The study demonstrates the feasibility of this novel genome editing approach to achieve functional control of HIV.

Sangamo BioSciences, Inc.

Additional data on the ongoing SB-728-T ongoing clinical trials in HIV will be presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2014), which is taking place in Boston, March 3-6, 2014.

"We have used Sangamo's ZFN technology to safely genetically engineer an HIV-infected individual's own T-cells and to make those cells resistant to infection by the virus," said Carl June, M.D., Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine at the Perelman School of Medicine at the University of Pennsylvania, and a senior author of the paper.  "This study demonstrates that ZFN-modified cells can be safely administered back to the individual; are able to persist and circulate throughout the body to key reservoirs of HIV infection; and show preferential survival over unmodified cells when antiviral drugs are withdrawn, potentially keeping the virus under control without the use of drugs. Our experience reinforces our belief that an immunological approach is a promising approach to enable functional control of HIV infection and eliminate the need for lifelong ART."

Summary of Study Results
In the study, T-cells from HIV subjects were isolated and edited with ZFNs to make them resistant to the virus by knocking out the CCR5 gene which encodes a coreceptor required for HIV infection.  After modification, the cells (SB-728-T) were returned to the subject, in a so-called "autologous infusion," and subjects were monitored for safety and a variety of immunological parameters.  The modified cells readily engrafted and were able to traffic throughout the body to key sites of HIV persistence such as the gut-associated lymphoid tissue. The data demonstrate that the modified cells persist and moreover appear to have a selective advantage, showing a preferential survival compared to unmodified cells when exposed to HIV during a planned interruption of ART. SB-728-T treatment was associated with an increase in the levels of total circulating CD4 T-cells and was well tolerated.

One of six subjects undergoing a treatment interruption experienced the longest delay in rebound of viral load when ART was withdrawn and achieved a decrease in VL to undetectable levels during the 12-week period. This subject was later found to carry a natural mutation of CCR5, CCR5 delta-32, in one of the two CCR5 genes (making the individual a CCR5 delta-32 heterozygote).  Thus, following exposure to the ZFNs targeting CCR5, at baseline this subject to had a greater percentage of T-cells that were modified at both sites (biallelic modification) and were fully resistant to HIV infection. Preliminary analyses suggest that the levels of circulating cells with biallelic modification of CCR5 may correlate with control of viral load.  Sangamo has ongoing clinical studies in CCR5 delta-32 heterozygotes (SB-728-902, Cohort 5) and in subjects undergoing Cytoxan pre-conditioning (SB-728-1101) to further study this relationship.

"The publication of this study in the New England Journal of Medicine represents a milestone in the development of ZFN-mediated genome editing as a new therapeutic approach," stated Edward Lanphier, Sangamo's president and chief executive officer. "Our ZFN technology functions at the DNA level, enabling us to make precise and persistent changes to the properties of cells that result in therapeutic benefit. Our goal is to use this powerful technology to engineer genetic cures for diseases that have thus far been treated as chronic conditions, including HIV and a wide range of monogenic diseases. The study represents an important first step in our development of this novel immunological therapy for HIV.  However, we now have clinical data from additional trials that confirm and extend the data presented in this early clinical trial.  We look forward to providing an update on our ongoing clinical trials at CROI and to providing guidance as to the future direction of this program."

Study Design
The study was an open-label, Phase 1 study of a single dose of approximately 10 billion ZFN-modified autologous T-cells in 12 HIV-infected subjects whose virus was well controlled by antiretroviral medications. Subjects were divided into two cohorts of six subjects each. Subjects in Cohort 1 were identified as immune responders who had demonstrated adequate recovery of CD4 T-cells after ART (>450 cells /mm3).Subjects in Cohort 2 were identified as individuals who had demonstrated inadequate recovery of CD4 T-cells after ART (200-500 cells /mm3), so-called immunologic non-responders.  Four weeks after SB-728-T treatment, Cohort 1 subjects underwent an interruption from ART of up to 12 weeks.  Cohort 2 remained on their ART throughout the study. The primary objective of the study was to assess safety and tolerability of administration of a single dose of SB-728-T.  Secondary outcomes included measures of immune reconstitution and HIV resistance. The study was carried out at the Hospital of the University of Pennsylvania and the Jacobi Medical Center, Albert Einstein College of Medicine and was supported in part by an NIAID Program Project Grant.

N.Eng. J. Med. 2014: 370:897-906 "Gene Editing of CCR5 in Autologous CD4 T-cells of Persons Infected with HIV." In addition to scientists and clinicians Perelman School of Medicine at the University of Pennsylvania, coauthors included researchers from the Albert Einstein School of Medicine and Sangamo BioSciences. Dr. June reports no financial disclosures related to Sangamo BioSciences.

About SB-728-T
SB-728-T is an autologous CD4+ T-cell product in which the gene for CCR5, a co-receptor for HIV entry, is modified via ZFN-mediated genome editing to disrupt the CCR5 protein.  T-cells with a disrupted CCR5 protein are resistant to infection by the most common strain of HIV.

About Sangamo
Sangamo BioSciences, Inc. is focused on Engineering Genetic CuresTM for monogenic and infectious diseases by deploying its novel DNA-binding protein technology platform in therapeutic gene regulation and genome editing. The Company has ongoing Phase 2 clinical trials to evaluate the safety and efficacy of a novel ZFP Therapeutic® for the treatment of HIV/AIDS (SB-728-T) and NGF-AAV for Alzheimer's disease (CERE-110). Sangamo's other therapeutic programs are focused on monogenic and rare diseases.  The company has formed a strategic collaboration with Shire International GmbH to develop therapeutics for hemophilia, Huntington's disease and other monogenic diseases, and with Biogen Idec for hemoglobinopathies, such as sickle cell disease and beta-thalassemia. It has also established strategic partnerships with companies in non-therapeutic applications of its technology, including Dow AgroSciences and Sigma-Aldrich Corporation. For more information about Sangamo, visit the Company's website at

ZFP Therapeutic® is a registered trademark of Sangamo BioSciences, Inc.

This press release may contain forward-looking statements based on Sangamo's current expectations. These forward-looking statements include, without limitation, references relating to research and development of novel ZFP TFs and ZFNs and therapeutic applications of Sangamo's ZFP technology platform for the treatment of HIV/AIDS, including a potential functional cure for HIV/AIDS, the ability of a ZFP Therapeutic to control HIV infection and projected timing of release of SB-728-T clinical data. Actual results may differ materially from these forward-looking statements due to a number of factors, including uncertainties relating to the initiation and completion of stages of our clinical trials, whether the clinical trials will validate and support the tolerability and efficacy of ZFNs, technological challenges, Sangamo's ability to develop commercially viable products and technological developments by our competitors. For a more detailed discussion of these and other risks, please see Sangamo's public filings with the Securities and Exchange Commission, including the risk factors described in its Annual Report on Form 10-K and its most recent Quarterly Report on Form 10-Q. Sangamo assumes no obligation to update the forward-looking information contained in this press release.

Logo -

SOURCE Sangamo BioSciences, Inc.

More Stories By PR Newswire

Copyright © 2007 PR Newswire. All rights reserved. Republication or redistribution of PRNewswire content is expressly prohibited without the prior written consent of PRNewswire. PRNewswire shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon.

Latest Stories
In his session at DevOps Summit, Bryan Cantrill, CTO at Joyent, will demonstrate a third path: containers on multi-tenant bare metal that maximizes performance, security, and networking connectivity.
DevOps has often been described in terms of CAMS: Culture, Automation, Measuring, Sharing. While we’ve seen a lot of focus on the “A” and even on the “M”, there are very few examples of why the “C" is equally important in the DevOps equation. In her session at @DevOps Summit, Lori MacVittie, of F5 Networks, will explore HTTP/1 and HTTP/2 along with Microservices to illustrate why a collaborative culture between Dev, Ops, and the Network is critical to ensuring success.
Manufacturing has widely adopted standardized and automated processes to create designs, build them, and maintain them through their life cycle. However, many modern manufacturing systems go beyond mechanized workflows to introduce empowered workers, flexible collaboration, and rapid iteration. Such behaviors also characterize open source software development and are at the heart of DevOps culture, processes, and tooling.
The IoT is upon us, but today’s databases, built on 30-year-old math, require multiple platforms to create a single solution. Data demands of the IoT require Big Data systems that can handle ingest, transactions and analytics concurrently adapting to varied situations as they occur, with speed at scale. In his session at @ThingsExpo, Chad Jones, chief strategy officer at Deep Information Sciences, will look differently at IoT data so enterprises can fully leverage their IoT potential. He’ll sha...
Containers have changed the mind of IT in DevOps. They enable developers to work with dev, test, stage and production environments identically. Containers provide the right abstraction for microservices and many cloud platforms have integrated them into deployment pipelines. DevOps and Containers together help companies to achieve their business goals faster and more effectively.
Today’s connected world is moving from devices towards things, what this means is that by using increasingly low cost sensors embedded in devices we can create many new use cases. These span across use cases in cities, vehicles, home, offices, factories, retail environments, worksites, health, logistics, and health. These use cases rely on ubiquitous connectivity and generate massive amounts of data at scale. These technologies enable new business opportunities, ways to optimize and automate, al...
The buzz continues for cloud, data analytics and the Internet of Things (IoT) and their collective impact across all industries. But a new conversation is emerging - how do companies use industry disruption and technology enablers to lead in markets undergoing change, uncertainty and ambiguity? Organizations of all sizes need to evolve and transform, often under massive pressure, as industry lines blur and merge and traditional business models are assaulted and turned upside down. In this new da...
Containers are revolutionizing the way we deploy and maintain our infrastructures, but monitoring and troubleshooting in a containerized environment can still be painful and impractical. Understanding even basic resource usage is difficult - let alone tracking network connections or malicious activity. In his session at DevOps Summit, Gianluca Borello, Sr. Software Engineer at Sysdig, will cover the current state of the art for container monitoring and visibility, including pros / cons and li...
SYS-CON Events announced today that IBM Cloud Data Services has been named “Bronze Sponsor” of SYS-CON's 17th Cloud Expo, which will take place on November 3–5, 2015, at the Santa Clara Convention Center in Santa Clara, CA. IBM Cloud Data Services offers a portfolio of integrated, best-of-breed cloud data services for developers focused on mobile computing and analytics use cases.
The Internet of Things (IoT) is growing rapidly by extending current technologies, products and networks. By 2020, Cisco estimates there will be 50 billion connected devices. Gartner has forecast revenues of over $300 billion, just to IoT suppliers. Now is the time to figure out how you’ll make money – not just create innovative products. With hundreds of new products and companies jumping into the IoT fray every month, there’s no shortage of innovation. Despite this, McKinsey/VisionMobile data...
Too often with compelling new technologies market participants become overly enamored with that attractiveness of the technology and neglect underlying business drivers. This tendency, what some call the “newest shiny object syndrome,” is understandable given that virtually all of us are heavily engaged in technology. But it is also mistaken. Without concrete business cases driving its deployment, IoT, like many other technologies before it, will fade into obscurity.
As the world moves towards more DevOps and microservices, application deployment to the cloud ought to become a lot simpler. The microservices architecture, which is the basis of many new age distributed systems such as OpenStack, NetFlix and so on, is at the heart of Cloud Foundry - a complete developer-oriented Platform as a Service (PaaS) that is IaaS agnostic and supports vCloud, OpenStack and AWS. In his session at 17th Cloud Expo, Raghavan "Rags" Srinivas, an Architect/Developer Evangeli...
There are many considerations when moving applications from on-premise to cloud. It is critical to understand the benefits and also challenges of this migration. A successful migration will result in lower Total Cost of Ownership, yet offer the same or higher level of robustness. Migration to cloud shifts computing resources from your data center, which can yield significant advantages provided that the cloud vendor an offer enterprise-grade quality for your application.
Today air travel is a minefield of delays, hassles and customer disappointment. Airlines struggle to revitalize the experience. GE and M2Mi will demonstrate practical examples of how IoT solutions are helping airlines bring back personalization, reduce trip time and improve reliability. In their session at @ThingsExpo, Shyam Varan Nath, Principal Architect with GE, and Dr. Sarah Cooper, M2Mi's VP Business Development and Engineering, will explore the IoT cloud-based platform technologies driv...
SYS-CON Events announced today that Sandy Carter, IBM General Manager Cloud Ecosystem and Developers, and a Social Business Evangelist, will keynote at the 17th International Cloud Expo®, which will take place on November 3–5, 2015, at the Santa Clara Convention Center in Santa Clara, CA.