Promising start to CIRM-funded trial for life-threatening blood disorder

Aristotle

At CIRM we are always happy to highlight success stories, particularly when they involve research we are funding. But we are also mindful of the need not to overstate a finding. To quote the Greek philosopher Aristotle (who doesn’t often make an appearance on this blog), “one swallow does not a summer make”. In other words, one good result doesn’t mean you have proven something works.  But it might mean that you are on the right track. And that’s why we are welcoming the news about a clinical trial we are funding with Sangamo Therapeutics.  

The trial is for the treatment of beta-thalassemia, (beta-thal) a severe form of anemia caused by a genetic mutation. People with beta-thal require life-long blood transfusions because they have low levels of hemoglobin, a protein needed to help the blood carry oxygen around the body. Those low levels of oxygen can cause anemia, fatigue, weakness and, in severe cases, can lead to organ damage and even death. The life expectancy for people with the more severe forms of the condition is only 30-50 years.

In this clinical trial the Sangamo team takes a patient’s own blood stem cells and, using a gene-editing technology called zinc finger nuclease (ZFN), inserts a working copy of the defective hemoglobin gene. These modified cells are given back to the patient, hopefully generating a new, healthy, blood supply which potentially will eliminate the need for chronic blood transfusions.

Yesterday, Sangamo announced that the first patient treated in this clinical trial seems to be doing rather well.

The therapy, called ST-400, was given to a patient who has the most severe form of beta-thal. In the two years before this treatment the patient was getting a blood transfusion every other week. While the treatment initially caused an allergic reaction, the patient quickly rebounded and in the seven weeks afterwards:

  • Demonstrated evidence of being able to produce new blood cells including platelets and white blood cells
  • Showed that the genetic edits made by ST-400 were found in new blood cells
  • Hemoglobin levels – the amount of oxygen carried in the blood – improved.

In the first few weeks after the therapy the patient needed some blood transfusions but in the next five weeks didn’t need any.

Obviously, this is encouraging. But it’s also just one patient. We don’t yet know if this will continue to help this individual let alone help any others. A point Dr. Angela Smith, one of the lead researchers on the project, made in a news release:

“While these data are very early and will require confirmation in additional patients as well as longer follow-up to draw any clinical conclusion, they are promising. The detection of indels in peripheral blood with increasing fetal hemoglobin at seven weeks is suggestive of successful gene editing in this transfusion-dependent beta thalassemia patient. These initial results are especially encouraging given the patient’s β0/ β0 genotype, a patient population which has proved to be difficult-to-treat and where there is high unmet medical need.” It’s a first step. But a promising one. And that’s always a great way to start.

Therapies Targeting Cancer, Deadly Immune Disorder and Life-Threatening Blood Condition Get Almost $32 Million Boost from CIRM Board

An innovative therapy that uses a patient’s own immune system to attack cancer stem cells is one of three new clinical trials approved for funding by CIRM’s Governing Board.

Researchers at the Stanford University School of Medicine were awarded $11.9 million to test their Chimeric Antigen Receptor (CAR) T Cell Therapy in patients with B cell leukemias who have relapsed or are not responding after standard treatments, such as chemotherapy.CDR774647-750Researchers take a patient’s own T cells (a type of immune cell) and genetically re-engineer them to recognize two target proteins on the surface of cancer cells, triggering their destruction. In addition, some of the T cells will form memory stem cells that will survive for years and continue to survey the body, killing any new or surviving cancer cells.

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Maria T. Millan

“When a patient is told that their cancer has returned it can be devastating news,” says Maria T. Millan, MD, President & CEO of CIRM. “CAR T cell therapy is an exciting and promising new approach that offers us a way to help patients fight back against a relapse, using their own cells to target and destroy the cancer.”

 

 

Sangamo-logoThe CIRM Board also approved $8 million for Sangamo Therapeutics, Inc. to test a new therapy for beta-thalassemia, a severe form of anemia (lack of healthy red blood cells) caused by mutations in the beta hemoglobin gene. Patients with this genetic disorder require frequent blood transfusions for survival and have a life expectancy of only 30-50 years. The Sangamo team will take a patient’s own blood stem cells and, using a gene-editing technology called zinc finger nuclease (ZFN), turn on a different hemoglobin gene (gamma hemoglobin) that can functionally substitute for the mutant gene. The modified blood stem cells will be given back to the patient, where they will give rise to functional red blood cells, and potentially eliminate the need for chronic transfusions and its associated complications.

UCSFvs1_bl_a_master_brand@2xThe third clinical trial approved is a $12 million grant to UC San Francisco for a treatment to restore the defective immune system of children born with severe combined immunodeficiency (SCID), a genetic blood disorder in which even a mild infection can be fatal. This condition is also called “bubble baby disease” because in the past children were kept inside sterile plastic bubbles to protect them from infection. This trial will focus on SCID patients who have mutations in a gene called Artemis, the most difficult form of SCID to treat using a standard bone marrow transplant from a healthy donor. The team will genetically modify the patient’s own blood stem cells with a functional copy of Artemis, with the goal of creating a functional immune system.

CIRM has funded two other clinical trials targeting different approaches to different forms of SCID. In one, carried out by UCLA and Orchard Therapeutics, 50 children have been treated and all 50 are considered functionally cured.

This brings the number of clinical trials funded by CIRM to 48, 42 of which are active. There are 11 other projects in the clinical trial stage where CIRM funded the early stage research.

Throwback Thursday: Progress towards a cure for HIV/AIDS

Welcome to our “Throwback Thursday” series on the Stem Cellar. Over the years, we’ve accumulated an arsenal of exciting stem cell stories about advances towards stem cell-based cures for serious diseases. Today we’re featuring stories about the progress of CIRM-funded research and clinical trials that are aimed at developing stem cell-based treatments for HIV/AIDS.

 Tomorrow, December 1st, is World AIDS Day. In honor of the 34 million people worldwide who are currently living with HIV, we’re dedicating our latest #ThrowbackThursday blog to the stem cell research and clinical trials our Agency is funding for HIV/AIDS.

world_logo3To jog your memory, HIV is a virus that hijacks your immune cells. If left untreated, HIV can lead to AIDS – a condition where your immune system is compromised and cannot defend your body against infection and diseases like cancer. If you want to read more background about HIV/AIDs, check out our disease fact sheet.

Stem Cell Advancements in HIV/AIDS
While patients can now manage HIV/AIDS by taking antiretroviral therapies (called HAART), these treatments only slow the progression of the disease. There is no effective cure for HIV/AIDS, making it a significant unmet medical need in the patient community.

CIRM is funding early stage research and clinical stage research projects that are developing cell based therapies to treat and hopefully one day cure people of HIV. So far, our Agency has awarded 17 grants totalling $72.9 million in funding to HIV/AIDS research. Below is a brief description of four of these exciting projects:

Discovery Stage Research
Dr. David Baltimore at the California Institute of Technology is developing an innovative stem cell-based immunotherapy that would prevent HIV infection in specific patient populations. He recently received a CIRM Quest award, (a funding initiative in our Discovery Stage Research Program) to pursue this research.

CIRM science officer, Dr. Ross Okamura, oversees Baltimore’s CIRM grant. He explained how the Baltimore team is genetically modifying the blood stem cells of patients so that they develop into immune cells (called T cells) that specifically recognize and target the HIV virus.

Ross_IDCard

Ross Okamura, PhD

“The approach Dr. Baltimore is taking in his CIRM Discovery Quest award is to engineer human immune stem cells to suppress HIV infection.  He is providing his engineered cells with T cell protein receptors that specifically target HIV and then exploring if he can reduce the viral load of HIV (the amount of virus in a specific volume) in an animal model of the human immune system. If successful, the approach could provide life-long protection from HIV infection.”

While Baltimore’s team is currently testing this strategy in mice, if all goes well, their goal is to translate this strategy into a preventative HIV therapy for people.

Clinical Trials
CIRM is currently funding three clinical trials focused on HIV/AIDS led by teams at Calimmune, City of Hope/Sangamo Biosciences and UC Davis. Rather than spelling out the details of each trial, I’ll refer you to our new Clinical Trial Dashboard (a screenshot of the dashboard is below) and to our new Blood & Immune Disorders clinical trial infographic we released in October.

dashboardblooddisorders

MonthofCIRM_BloodDisordersJustHIV.png

As you can see from these projects, CIRM is committed to funding cutting edge research in HIV/AIDS. We hope that in the next few years, some of these projects will bear fruit and help advance stem cell-based therapies to patients suffering from this disease.

I’ll leave you with a few links to other #WorldAIDSDay relevant blogs from our Stem Cellar archive and our videos that are worth checking out.

 

CIRM-Funded Clinical Trials Targeting Blood and Immune Disorders

This blog is part of our Month of CIRM series, which features our Agency’s progress towards achieving our mission to accelerate stem cell treatments to patients with unmet medical needs.

This week, we’re highlighting CIRM-funded clinical trials to address the growing interest in our rapidly expanding clinical portfolio. Today we are featuring trials in our blood and immune disorders portfolio, specifically focusing on sickle cell disease, HIV/AIDS, severe combined immunodeficiency (SCID, also known as bubble baby disease) and rare disease called chronic granulomatous disease (CGD).

CIRM has funded a total of eight trials targeting these disease areas, all of which are currently active. Check out the infographic below for a list of those trials.

For more details about all CIRM-funded clinical trials, visit our clinical trials page and read our clinical trials brochure which provides brief overviews of each trial.

Key Steps Along the Way To Finding Treatments for HIV on World AIDS Day

Today, December 1st,  is World AIDS Day. It’s a day to acknowledge the progress that is being made in HIV prevention and treatment around the world but also to renew our commitment to a future free of HIV. This year’s theme is Leadership. Commitment. Impact.  At CIRM we are funding a number of projects focused on HIV/AIDS, so we asked Jeff Sheehy, the patient advocate for HIV/AIDS on the CIRM Board to offer his perspective on the fight against the virus.

jeff-sheehy

At CIRM we talk about and hope for cures, but our actual mission is “accelerating stem cell treatments to patients with unmet medical needs.”

For those of us in the HIV/AIDS community, we are tremendously excited about finding a cure for HIV.  We have the example of Timothy Brown, aka the “Berlin Patient”, the only person cured of HIV.

Multiple Shots on Goal

Different approaches to a cure are under investigation with multiple clinical trials.  CIRM is funding three clinical trials using cell/gene therapy in attempts to genetically modify blood forming stem cells to resist infection with HIV.  While we hope this leads to a cure, community activists have come together to urge a look at something short of a “home run.”

A subset of HIV patients go on treatment, control the virus in their blood to the point where it can’t be detected by common diagnostic tests, but never see their crucial immune fighting CD4 T cells return to normal levels after decimation by HIV.

For instance, I have been on antiretroviral therapy since 1997.  My CD4 T cells had dropped precipitously, dangerous close to the level of 200.  At that level, I would have had an AIDS diagnosis and would have been extremely vulnerable to a whole host of opportunistic infections.  Fortunately, my virus was controlled within a few weeks and within a year, my CD T cells had returned to normal levels.

For the immunological non-responders I described above, that doesn’t happen.  So while the virus is under control, their T cell counts remain low and they are very susceptible to opportunistic infections and are at much greater risk of dying.

Immunological non-responders (INRs) are usually patients who had AIDS when they were diagnosed, meaning they presented with very low CD4 T cell counts.  Many are also older.  We had hoped that with frequent testing, treatment upon diagnosis and robust healthcare systems, this population would be less of a factor.  Yet in San Francisco with its very comprehensive and sophisticated testing and treatment protocols, 16% of newly diagnosed patients in 2015 had full blown AIDS.

Until we make greater progress in testing and treating people with HIV, we can expect to see immunological non-responders who will experience sub-optimal health outcomes and who will be more difficult to treat and keep alive.

Boosting the Immune System

A major cell/gene trial for HIV targeted this population.  Their obvious unmet medical need and their greater morbidity/mortality balanced the risks of first in man gene therapy.  Sangamo, a CIRM grantee, used zinc finger nucleases to snip out a receptor, CCR5, on the surface of CD4 T cells taken from INR patients.  That receptor is a door that HIV uses to enter cells.  Some people naturally lack the receptor and usually are unable to be infected with HIV.  The Berlin Patient had his entire immune system replaced with cells from someone lacking CCR5.

Most of the patients in that first trial saw their CD4 T cells rise sharply.  The amount of HIV circulating in their gut decreased.  They experienced a high degree of modification and persistence in T stem cells, which replenish the T cell population.  And most importantly, some who regularly experienced opportunistic infections such as my friend and study participant Matt Sharp who came down with pneumonia every winter, had several healthy seasons.

Missed Opportunities

Unfortunately, the drive for a cure pushed development of the product in a different direction.  This is in large part to regulatory challenges.  A prior trial started in the late 90’s by Chiron tested a cytokine, IL 2, to see if administering it could increase T cells.  It did, but proving that these new T cells did anything was illusive and development ceased.  Another cytokine, IL 7, was moving down the development pathway when the company developing it, Cytheris, ceased business.  The pivotal trial would have required enrolling 4,000 participants, a daunting and expensive prospect.  This was due to the need to demonstrate clinical impact of the new cells in a diverse group of patients.

Given the unmet need, HIV activists have looked at the Sangamo trial, amongst others, and have initiated a dialogue with the FDA.  Activists are exploring seeking orphan drug status since the population of INRs is relatively small.

Charting a New Course

They have also discussed trial designs looking at markers of immune activity and discussed potentially identifying a segment of INRs where clinical efficacy could be shown with far, far fewer participants.

Activists are calling for companies to join them in developing products for INRs.  I’ve included the press release issued yesterday by community advocates below.

With the collaboration of the HIV activist community, this could be a unique opportunity for cell/gene companies to actually get a therapy through the FDA. On this World AIDS Day, let’s consider the value of a solid single that serves patients in need while work continues on the home run.

NEWS RELEASE: HIV Activists Seek to Accelerate Development of Immune Enhancing Therapies for Immunologic Non-Responders.

Dialogues with FDA, scientists and industry encourage consideration of orphan drug designations for therapies to help the immunologic non-responder population and exploration of novel endpoints to reduce the size of efficacy trials.

November 30, 2016 – A coalition of HIV/AIDS activists are calling for renewed attention to HIV-positive people termed immunologic non-responders (INRs), who experience sub-optimal immune system reconstitution despite years of viral load suppression by antiretroviral therapy. Studies have shown that INR patients remain at increased risk of illness and death compared to HIV-positive people who have better restoration of immune function on current drug therapies. Risk factors for becoming an INR include older age and a low CD4 count at the time of treatment initiation. To date, efforts to develop immune enhancing interventions for this population have proven challenging, despite some candidates from small companies showing signs of promise.

“We believe there is an urgent need to find ways to encourage and accelerate development of therapies to reduce the health risks faced by INR patients,” stated Nelson Vergel of the Program for Wellness Restoration (PoWeR), who initiated the activist coalition. “For example, Orphan Drug designations[i] could be granted to encourage faster-track approval of promising therapies.  These interventions may eventually help not only INRs but also people with other immune deficiency conditions”.

Along with funding, a major challenge for approval of any potential therapy is proving its efficacy. While INRs face significantly increased risk of serious morbidities and mortality compared to HIV-positive individuals with more robust immune reconstitution, demonstrating a reduction in the incidence of these outcomes would likely require expensive and lengthy clinical trials involving thousands of individuals. Activists are therefore encouraging the US Food & Drug Administration (FDA), industry and researchers to evaluate potential surrogate markers of efficacy such as relative improvements in clinical problems that may be more frequent in INR patients, such as upper respiratory infections, gastrointestinal disease, and other health issues.

“Given the risks faced by INR patients, every effort should be made to assess whether less burdensome pathways toward approval are feasible, without compromising the regulatory requirement for compelling evidence of safety and efficacy”, said Richard Jefferys of the Treatment Action Group.

The coalition is advocating that scientists, biotech and pharmaceutical companies pursue therapeutic candidates for INRs. For example, while gene and anti-inflammatory therapies for HIV are being assessed in the context of cure research, there is also evidence that they may have potential to promote immune reconstitution and reduce markers associated with risk of morbidity and mortality in INR patients. Therapeutic research should also be accompanied by robust study of the etiology and mechanisms of sub-optimal immune responses.

“While there is, appropriately, a major research focus on curing HIV, we must be alert to evidence that candidate therapies could have benefits for INR patients, and be willing to study them in this context”, argued Matt Sharp, a coalition member and INR who experienced enhanced immune reconstitution and improved health and quality of life after receiving an experimental gene therapy.

The coalition has held an initial conference call with FDA to discuss the issue. Minutes are available online.

The coalition is now aiming to convene a broader dialogue with various drug companies on the development of therapies for INR patients. Stakeholders who are interested in becoming involved are encouraged to contact coalition representatives.

[i] The Orphan Drug Act incentivizes the development of treatments for rare conditions. For more information, see:  http://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/ucm2005525.htm

For more information:

Richard Jefferys

Michael Palm Basic Science, Vaccines & Cure Project Director
Treatment Action Group richard.jefferys@treatmentactiongroup.org

Nelson Vergel, Program for Wellness Restoration programforwellness@gmail.com

 

 

HIV/AIDS: Progress and Promise of Stem Cell Research

Our friends at Americans for Cures and Youreka Science have done it again. They’ve produced another whiteboard video about the progress and promise of stem cell research that’s so inspiring that it would probably make Darth Vader consider coming back to the light side. This time they tackled HIV.

If you haven’t watched one of these videos already, let me bring you up to speed. Americans for Cures is a non-profit organization, the legacy of the passing of Proposition 71, that supports patient advocates in the fight for stem cell research and cures. They’ve partnered with Youreka Science to produce eye-catching and informative videos to teach patients and the general public about the current state of stem cell research and the quest for cures for major diseases.

Stem cell cure for HIV?

Their latest video is on HIV, a well-known and deadly virus that attacks and disables the human immune system. Currently, 37 million people globally are living with HIV and only a few have been cured.

The video begins with the story of Timothy Brown, also known as the Berlin patient. In 2008 at the age of 40, he was dying of a blood cancer called acute myeloid leukemia and needed a bone marrow stem cell transplant to survive. Timothy was also HIV positive, so his doctor decided to use a bone marrow donor who happened to be naturally resistant to HIV infection. The transplanted donor stem cells were not only successful in curing Timothy of his cancer, but they also “rebooted his immune system” and cured his HIV.

Screen Shot 2015-12-23 at 2.21.18 PMSo why haven’t all HIV patients received this treatment? The video goes on to explain that bone marrow transplants are dangerous and only used in cancer patients who’ve run out of options. Additionally, only a small percentage of the world’s population is resistant to HIV and the chances that one of these individuals is a bone marrow donor match to a patient is very low.

This is where science comes to the rescue. Three research groups in California, all currently supported by CIRM funding, have proposed alternative solutions: they are attempting to make a patient’s own immune system resistant to HIV instead of relying on donor stem cells. Using gene therapy, they are modifying blood stem cells from HIV patients to be HIV resistant, and then transplanting the modified stem cells back into the same patient to rebuild a new immune system that can block HIV infection.

Screen Shot 2015-12-23 at 4.47.17 PM

All three groups have proven their stem cell technology works in animals; two of them are now testing their approach in early phase clinical trials in humans, and one is getting ready to do so. If these trials are successful, there is good reason to hope for an HIV cure and maybe even cures for other immune diseases.

My thoughts…

What I liked most about this video was the very end. It concludes by saying that these accomplishments were made possible not just by funding promising scientific research, but also by the hard work of HIV patients and patient advocate communities, who’ve brought awareness to the disease and influenced policy changes. Ultimately, a cure for HIV will depend on researchers and patient advocates working together to push the pace and to tackle any obstacles that will likely appear with testing stem cell therapies in human clinical trials.

I couldn’t say it any better than the final line of the video:

“We must remember that human trials will celebrate successes, but barriers will surface along with complications and challenges. So patience and understanding of the scientific process are essential.”

Gene editing in blood stem cells just got easier

Genome editing is a field of science that’s been around for awhile, but has experienced an explosion of activity and interest in recent years. Chances are that even your grandmother has heard about the recent story where for the first time, gene editing saved a one-year-old girl from dying of leukemia.

Microsoft word versus genome editing

To give you an idea of what this technique involves, think back to the last time you had to write a report. You let all your ideas flow out onto the page, but then realize that certain sentences or paragraphs need to be rearranged, removed, or added. So you copy, paste, and move stuff around with your mouse and keyboard until you’re satisfied.

Image source: Broad Institute

Image source: Broad Institute

Tools for editing the genome (which contain all of our genes) work a similar way, but they cut and paste DNA sequences in the human genome instead of words on a page. Scientists have figured out how to use these “genetic scissors” to delete genes (so they no longer have function) and to correct disease-causing mutations (by pasting in the normal DNA sequence of a gene to restore function). Both these abilities make genome editing a highly valuable tool for scientists to model diseases and to develop therapies to treat them.

There are multiple tools that researchers are currently using to modify the human genome. The main ones are fancifully named ZFNs, TALENs, and CRISPRs. All three use engineered proteins called nucleases to cut strands of DNA at specific locations in the genome. A cell’s DNA repair machinery will then either glue the DNA strands back together (this typically results in the loss of DNA and gene function), or repair the break by copying and pasting in the missing sequence of DNA from a template (you can correct disease-causing mutations this way by providing a donor template). We don’t have time to get into more details about how these tools work, but you can learn more by reading this fact sheet from Science Media Centre.

Some cells are more stubborn than others

While genome editing technologies offer many advantages for modifying human genes, it’s not a perfect science. There are still many limitations and roadblocks that need to be addressed to make sure that these tools can be safely and effectively used as therapies in humans.

Besides the obvious worry about “off-target effects” (when the genetic scissors cut random sections of DNA, which can cause big problems), another issue with genome editing tools is that some types of cells are harder to genetically modify than others.

Such is the case with blood stem cells, also known as hematopoietic stem and progenitor cells (HSPCs), that live in our bone marrow and make all the different blood cells in our body. Initial studies reported difficulty in delivering genome editing tools into human HSPCs, which is a problem if you want to use these tools to help cure patients suffering from genetic blood or immune diseases.

Human blood (red) and immune cells (green) are made from hematopoietic/blood stem cells. Photo credit: ZEISS Microscopy.

Human blood (red) and immune cells (green) are made from hematopoietic/blood stem cells. Photo credit: ZEISS Microscopy.

Have no fear, blood-stem cell editing is here

We are happy to inform you that a CIRM-funded study published today in Nature Biotechnology has developed a solution to the problem of hard-to-edit blood stem cells. Scientists from the USC Keck School of Medicine and from Sangamo BioSciences developed a new delivery method that allows for efficient genome editing of human HSPCs using zinc finger nucleases (ZFNs).

They used a viral delivery system to deliver ZFNs to distinct locations in the genome of HSPCs and successfully inserted a gene sequence that made the cells turn green under a fluorescent microscope. The virus they used was a harmless form of an adeno-associated virus (AAV), which can enter certain cells and delivery the researcher’s DNA cargo with a very low chance of altering or inserting its own DNA into the HSPC genome.

Using an AAV that was exceptionally good at entering HPSCs, they virally delivered ZFNs to specific gene locations in HSPCs that had been isolated from human blood and from fetal liver tissue. They found that delivering the ZFNs as mRNA molecules allowed the protein versions they turned into to be temporarily expressed in HSPCs. This produced a high rate of gene insertion (ranging from 15-40% of cells treated), while keeping off-target effects and cell death low. Even the most hard-to-edit HSPCs, called the primitive HSPCs, were modified. This result was really exciting because no other study has reported gene editing with this level of efficiency in this primitive population of blood stem cells.

The tools work but what about the cells?

After proving that they were able to successfully edit the genomes of HSPCs with high efficiency, they next asked whether the modified cells could grow in culture and create new blood cells when transplanted into mice.

While their method to deliver ZFNs into the HSPCs did cause some of the cells to die (around 20%), the majority that survived were able to multiply in a dish and specialize into various blood cells when grown in cultures. When the modified HSPCs were taken a step further and transplanted into immune-deficient mice (meaning their immune system is compromised and won’t attack transplanted cells), they not only survived, but they also specialized into many different types of blood cells while still retaining their genomic modifications.

Now here is where I want to give the researchers a high five. They decided that once wasn’t enough, and challenged their modified HSPCs to a second round of transplantation. They collected the bone marrow from mice that received the first transplant of modified HSPCs, and transferred it into another immune-deficient mouse. Five months later, they found that the modified cells were still there and had generated other blood cell types. Because these modified HSPCs lasted for so long and through two rounds of transplants, the authors concluded that they had successfully edited the primitive, long-term repopulating HSPCs.

Next stop, the clinic?

In summary, this study offers a new and improved method to genetically modify blood stem cells in all their forms.

So what’s next? The obvious hope is the clinic.

HIV (yellow) infecting a human immune cell. CREDIT: SETH PINCUS, ELIZABETH FISCHER AND AUSTIN ATHMAN, NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NATIONAL INSTITUTES OF HEALTH

HIV (yellow) infecting a human immune cell. Photo credit: Seth Pincus, Elizabeth Fischer and Austin Athman, NIH.

It’s a likely future as the study was conducted in collaboration with Sangamo BioSciences. They specialize in ZFN-mediated gene therapy and have a number of preclinical therapeutic programs, many of which focus on genetic diseases that affect the blood and immune system, as well as ongoing clinical trials using ZFNs to treat patients with HIV/AIDs. (One of these trials is funded by CIRM, read more here).

In a USC press release, Dr. Michael Holmes, VP of Research at Sangamo and co-senior author on the paper hinted at future clinical applications:

Michael Holmes, Sangamo BioSciences

Michael Holmes, Sangamo BioSciences

 

Our results provide a strategy for broadening the application of gene editing technologies in HSPCs. This significantly advances our progress towards applying gene editing to the treatment of human diseases of the blood and immune systems.

 

 

Co-senior author and USC Professor Dr. Paula Cannon echoed Dr. Holmes:

Gene therapy using HSPCs has enormous potential for treating HIV and other diseases of the blood and immune systems.

One last question

A question that I had after reading this exciting study was whether other genome editing tools such as CRISPR could produce better results in blood stem cells using a similar viral delivery method.

CRISPR is described as a faster, cheaper, and easier gene editing technology compared to ZFNs and TALENS (for a comparison, check out this fun article by The Jackson Laboratory). And many scientists, both in academia and industry, are pushing CRISPR gene editing towards clinical applications.

When I asked Paula Cannon about which gene editing technology, ZFNs or CRISPRs, is better for therapeutic development, she said:

Paula Cannon, USC Professor

Paula Cannon, USC Professor

In terms of advantages, CRISPRs are easier to work with initially, and this makes them a great lab research tool. But when it comes to developing something for a clinical trial, its much more of a long game, so that initial advantage disappears. The ZFNs I work with have been previously optimized and are well characterized, and the CCR5 ZFNs are already in the clinic so they have a big advantage in that regard when you are trying to develop something for the next clinical application.


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