We need a patient-first approach for any variant in any patient, whomever, wherever they are. Each and every patient deserves a fair shot at this!” exclaimed Kiran Musunuru, MD, PhD, as he held the crowd captive at the American Society of Gene & Cell Therapy (ASGCT) annual meeting in New Orleans last month.
Musunuru had just announced that the world’s first patient was treated with a personalized CRISPR gene editing therapy at Children’s Hospital of Philadelphia (CHOP).
Baby KJ, the first patient to be treated with a personalized CRISPR therapy, reaches out post-infusion. [Children’s Hospital of Philadelphia]
The infant, named KJ, was diagnosed with a rare metabolic disease known as severe carbamoyl phosphate synthetase 1 (CPS1) deficiency, an autosomal recessive disorder which causes toxic ammonia buildup in the blood. KJ was too young and vulnerable to receive a liver transplant, the only standard-of-care option for the disease, and with each day that passed, the episodes of increased ammonia put him at risk for ongoing neurological damage or death.
Musunuru, a cardiologist and professor for translational research at University of Pennsylvania School of Medicine, teamed up with Rebecca Ahrens-Nicklas, MD, PhD, assistant professor of Pediatrics at the University of Pennsylvania, regulators, and industry partners to manufacture a personalized base editing therapy designed to correct KJ’s individual mutation. The large collaborative effort led KJ to receive the first dose within a swift seven months.
Within seven weeks after infusion day, KJ was able to tolerate increased dietary protein and receive half the starting dose of his nitrogen-scavenger medication, putting him on a promising path of improvement.
While Ahrens-Nicklas emphasized that it is still early days to determine KJ’s long-term outlook, she highlights that he has made slow but steady progress. KJ is “safer than he was before” with the research team having “much more to learn from him.”
“We want each and every patient to have the potential to experience the same results we saw in this first patient,” said Musunuru. “The promise of gene therapy that we’ve heard about for decades is coming to fruition, and it’s going to utterly transform the way we approach medicine.”
Nobel laureate and CRISPR pioneer, Jennifer Doudna, PhD, aspires for
“CRISPR to become the standard of medical care for certain diseases” when asked for her dream for the technology in the next 5–10 years. That vision has slowly started to come to life.
Jennifer Doudna, PhD, giving opening remarks at CRISPR Cures Day. [Glenn Ramit]
KJ’s case follows the clinical success of Casgevy, a one-time gene therapy for treating sickle cell disease (SCD) and transfusion-dependent beta thalassemia and the first CRISPR-based therapy approved by the FDA. The drug was a collaborative effort between Vertex Pharmaceuticals and CRISPR Therapeutics and gave new hope to SCD patients who previously had no cure.
Additionally, many experts have eyed promising results from Intellia Therapeutics as the next contender for clinical approval. The Cambridge-based company’s pipeline includes demonstration of the first in vivo gene editing in humans for transthyretin (ATTR) amyloidosis with cardiomyopathy, a progressive disease characterized by buildup of protein fibrils in the heart. The first patient was dosed in a Phase III study last year.
Despite CRISPR’s promise, gene editing companies have found themselves in a challenging climate. Earlier this Spring, Peter Marks, MD, PhD, a key ally to the rare disease community who oversaw the approval of 22 gene therapies, resigned from his role as Director of the FDA’s Center for Biologics Evaluation and Research (CBER). His departure has left cell and gene therapy’s regulatory outlook uncertain.
Additionally, many gene editing startups are facing funding challenges leading to reduced staff and trimmed pipelines. In a bleak announcement last December, Editas Medicine, one of the first CRISPR companies founded in 2013, cut 65% of its employees. Additional companies followed suit, including Intellia, Aera Therapeutics, and Caribou Biosciences undergoing layoffs impacting over a quarter of their headcount.
Tome Biosciences, a once well-backed gene editing start-up that launched with $213 million in 2023, folded completely last year. Founded by Massachusetts Institute of Technology (MIT) duo, Omar Abudayyeh, PhD, and Jonathan Gootenberg, PhD, Tome’s technology sought to insert large DNA sequences into the genome, a proposed advance over most CRISPR methods which were limited to small edits.
Despite these trends, Benjamin Oakes, PhD, CEO of Scribe Therapeutics, says genetic medicine companies have comparatively held up better over a biotech downtown that’s “blown out the whole sector” for almost four years.
“The challenge comes from the broader market, but in reality, you’re seeing nothing but good data come out of the CRISPR space,” Oakes told GEN. “I don’t believe the ability to cure patients is going anywhere. We are all resistant to change, especially if it’s a change to the medical paradigm.”
Scribe is a Bay Area-based CRISPR gene editing company co-founded by Doudna. As natural CRISPR systems originate from bacteria, Scribe’s platform features a new CRISPR enzyme, termed CasX, which is engineered to improve the potency, specificity, and safety of gene editing in humans. Additionally, Scribe’s epigenetic silencing platform, termed Epigenetic Long-term X-Repressor (ELXR), turns off gene expression of multiple targets without cutting DNA.
Fyodor Urnov, PhD, director of technology and translation at the Innovative Genomics Institute (IGI), who recently authored a 6,000-word editorial in The CRISPR Journal to “give Cas a chance,” says there’s no magic want that enables a technology to change the world. Experiencing resistance when on route to public acceptance is not uncommon for a new therapeutic modality.
“CRISPR fundamentally can do what we wanted to do, but a good chunk of the regulatory environment, for example, putting CRISPR into a person, hasn’t changed in 15 years,” Urnov told me during my recent visit to the IGI earlier this Spring.
Amber Salzman, PhD, CEO of Epicrispr Biotechnologies, sees the shift as a more selective market, with investor interest in CRISPR and gene regulation remaining strong, especially for platforms with “differentiated science and clear clinical potential.”
“What we’re seeing isn’t a pullback, but a shift in focus. Investors are now looking for companies that can bridge from breakthrough science to real-world impact for companies with compelling data, well-defined pipelines, and a clear regulatory and commercial strategy,” Salzman told GEN.
As a new therapeutic modality, CRISPR therapy must establish its own research, manufacturing, regulatory, and commercial pipelines to achieve societal uptake, with delivery being one of the biggest barriers to the clinic.
To receive Casgevy’s ex vivo therapy, patients must undergo a bone marrow transplant, a brutal approach that is also expensive and difficult to scale. Additionally, KJ’s in vivo personalized CSP1 treatment targeted the liver, where the delivery challenge has largely been solved. Clinical proof points showing successful in vivo targeting to broader tissues have yet to come through the gate.
New early gene editing platforms are rising to address the in vivo challenge. In May, Stylus Medicine, co-founded by Patrick Hsu, PhD, core investigator at the Arc Institute, launched with $85 million to advance precise, durable CAR T generation inside the body. The company’s approach uses cell-targeted lipid nanoparticles (LNPs) to deliver therapeutic payloads directly to immune cells in vivo.
On the commercial side, CRISPR’s proposed paradigm shift to cure patients with a single treatment has historically left investors scratching their heads. Even if a new therapeutic modality “looks good in a lot of ways,” there remains uncertainty about commercial adoption, commented Erik Sontheimer, PhD, professor at the RNA Therapeutics Institute at UMass Chan Medical School in an interview with GEN.
To address these challenges, Sontheimer says collaboration with companies that have strong regulatory and commercial experience, in addition to a compatible approach and culture, goes a long way toward supporting long-term clinical success. He noted that synergistic pairings, such as CRISPR Therapeutics and Vertex, and Intellia and Regeneron, largely contributed to the success of Casgevy and the ATTR therapeutic program, respectively.
To support this mission, Danaher and the IGI launched the Danaher-IGI Beacon for CRISPR Cures program in early 2024 to produce a “stacked” manufacturing platform for gene editing therapies with the goal of increasing the number of patients treated with CRISPR-based technology from approximately 210 patients today to many thousands over the next decade.
In this collaboration, Danaher provides manufacturing and technological support to CRISPR therapy researchers within the IGI ecosystem by leveraging its more than 15 diverse businesses, including Integrated DNA Technologies (IDT), Cytiva, Molecular Devices, Leica, Beckman Coulter, and Aldevron.
This vision has translated into impact. Aldevron and IDT were among the crucial team that effectively manufactured KJ’s historic personalized CRISPR gene editing drug, which required a new guide RNA (gRNA) sequence, mRNA-encoded base editor, custom off-target safety services, and clinically validated lipid nanoparticle (LNP) formulation, all on a swift time scale of a few months.
“Our mission in academic science is to create new things and explore new ideas. What we’re not good at is developing ideas so that they can be widely available, affordable, and disseminated,” said Doudna at CRISPR Cures Day, a celebration of the collaboration’s one year anniversary hosted at the IGI in February. “This partnership is our effort to bring those two areas together so that CRISPR can have a global impact.”
While CRISPR is an “electric car in a universe that was built for early model internal combustion engines,” to use Urnov’s words, the promise of gene editing technology remains at the forefront. Time will tell how the power of collaborative minds will push the next wave of CRISPR cures to the clinic.
Read more in World’s First Patient Treated with Personalized CRISPR Therapy and First Personalized CRISPR Gene Editing Therapy Patient Baby KJ Discharged.
The post Advancing CRISPR Cures Requires Cross-Sector Collaboration appeared first on GEN - Genetic Engineering and Biotechnology News.
Musunuru had just announced that the world’s first patient was treated with a personalized CRISPR gene editing therapy at Children’s Hospital of Philadelphia (CHOP).
Baby KJ, the first patient to be treated with a personalized CRISPR therapy, reaches out post-infusion. [Children’s Hospital of Philadelphia]
The infant, named KJ, was diagnosed with a rare metabolic disease known as severe carbamoyl phosphate synthetase 1 (CPS1) deficiency, an autosomal recessive disorder which causes toxic ammonia buildup in the blood. KJ was too young and vulnerable to receive a liver transplant, the only standard-of-care option for the disease, and with each day that passed, the episodes of increased ammonia put him at risk for ongoing neurological damage or death.
Musunuru, a cardiologist and professor for translational research at University of Pennsylvania School of Medicine, teamed up with Rebecca Ahrens-Nicklas, MD, PhD, assistant professor of Pediatrics at the University of Pennsylvania, regulators, and industry partners to manufacture a personalized base editing therapy designed to correct KJ’s individual mutation. The large collaborative effort led KJ to receive the first dose within a swift seven months.
Within seven weeks after infusion day, KJ was able to tolerate increased dietary protein and receive half the starting dose of his nitrogen-scavenger medication, putting him on a promising path of improvement.
While Ahrens-Nicklas emphasized that it is still early days to determine KJ’s long-term outlook, she highlights that he has made slow but steady progress. KJ is “safer than he was before” with the research team having “much more to learn from him.”
“We want each and every patient to have the potential to experience the same results we saw in this first patient,” said Musunuru. “The promise of gene therapy that we’ve heard about for decades is coming to fruition, and it’s going to utterly transform the way we approach medicine.”
CRISPR challenges
Nobel laureate and CRISPR pioneer, Jennifer Doudna, PhD, aspires for
“CRISPR to become the standard of medical care for certain diseases” when asked for her dream for the technology in the next 5–10 years. That vision has slowly started to come to life.
Jennifer Doudna, PhD, giving opening remarks at CRISPR Cures Day. [Glenn Ramit]
KJ’s case follows the clinical success of Casgevy, a one-time gene therapy for treating sickle cell disease (SCD) and transfusion-dependent beta thalassemia and the first CRISPR-based therapy approved by the FDA. The drug was a collaborative effort between Vertex Pharmaceuticals and CRISPR Therapeutics and gave new hope to SCD patients who previously had no cure.
Additionally, many experts have eyed promising results from Intellia Therapeutics as the next contender for clinical approval. The Cambridge-based company’s pipeline includes demonstration of the first in vivo gene editing in humans for transthyretin (ATTR) amyloidosis with cardiomyopathy, a progressive disease characterized by buildup of protein fibrils in the heart. The first patient was dosed in a Phase III study last year.
Despite CRISPR’s promise, gene editing companies have found themselves in a challenging climate. Earlier this Spring, Peter Marks, MD, PhD, a key ally to the rare disease community who oversaw the approval of 22 gene therapies, resigned from his role as Director of the FDA’s Center for Biologics Evaluation and Research (CBER). His departure has left cell and gene therapy’s regulatory outlook uncertain.
Additionally, many gene editing startups are facing funding challenges leading to reduced staff and trimmed pipelines. In a bleak announcement last December, Editas Medicine, one of the first CRISPR companies founded in 2013, cut 65% of its employees. Additional companies followed suit, including Intellia, Aera Therapeutics, and Caribou Biosciences undergoing layoffs impacting over a quarter of their headcount.
Tome Biosciences, a once well-backed gene editing start-up that launched with $213 million in 2023, folded completely last year. Founded by Massachusetts Institute of Technology (MIT) duo, Omar Abudayyeh, PhD, and Jonathan Gootenberg, PhD, Tome’s technology sought to insert large DNA sequences into the genome, a proposed advance over most CRISPR methods which were limited to small edits.
Despite these trends, Benjamin Oakes, PhD, CEO of Scribe Therapeutics, says genetic medicine companies have comparatively held up better over a biotech downtown that’s “blown out the whole sector” for almost four years.
“The challenge comes from the broader market, but in reality, you’re seeing nothing but good data come out of the CRISPR space,” Oakes told GEN. “I don’t believe the ability to cure patients is going anywhere. We are all resistant to change, especially if it’s a change to the medical paradigm.”
Scribe is a Bay Area-based CRISPR gene editing company co-founded by Doudna. As natural CRISPR systems originate from bacteria, Scribe’s platform features a new CRISPR enzyme, termed CasX, which is engineered to improve the potency, specificity, and safety of gene editing in humans. Additionally, Scribe’s epigenetic silencing platform, termed Epigenetic Long-term X-Repressor (ELXR), turns off gene expression of multiple targets without cutting DNA.
Fyodor Urnov, PhD, director of technology and translation at the Innovative Genomics Institute (IGI), who recently authored a 6,000-word editorial in The CRISPR Journal to “give Cas a chance,” says there’s no magic want that enables a technology to change the world. Experiencing resistance when on route to public acceptance is not uncommon for a new therapeutic modality.
“CRISPR fundamentally can do what we wanted to do, but a good chunk of the regulatory environment, for example, putting CRISPR into a person, hasn’t changed in 15 years,” Urnov told me during my recent visit to the IGI earlier this Spring.
Amber Salzman, PhD, CEO of Epicrispr Biotechnologies, sees the shift as a more selective market, with investor interest in CRISPR and gene regulation remaining strong, especially for platforms with “differentiated science and clear clinical potential.”
“What we’re seeing isn’t a pullback, but a shift in focus. Investors are now looking for companies that can bridge from breakthrough science to real-world impact for companies with compelling data, well-defined pipelines, and a clear regulatory and commercial strategy,” Salzman told GEN.
Partner up
As a new therapeutic modality, CRISPR therapy must establish its own research, manufacturing, regulatory, and commercial pipelines to achieve societal uptake, with delivery being one of the biggest barriers to the clinic.
To receive Casgevy’s ex vivo therapy, patients must undergo a bone marrow transplant, a brutal approach that is also expensive and difficult to scale. Additionally, KJ’s in vivo personalized CSP1 treatment targeted the liver, where the delivery challenge has largely been solved. Clinical proof points showing successful in vivo targeting to broader tissues have yet to come through the gate.
New early gene editing platforms are rising to address the in vivo challenge. In May, Stylus Medicine, co-founded by Patrick Hsu, PhD, core investigator at the Arc Institute, launched with $85 million to advance precise, durable CAR T generation inside the body. The company’s approach uses cell-targeted lipid nanoparticles (LNPs) to deliver therapeutic payloads directly to immune cells in vivo.
On the commercial side, CRISPR’s proposed paradigm shift to cure patients with a single treatment has historically left investors scratching their heads. Even if a new therapeutic modality “looks good in a lot of ways,” there remains uncertainty about commercial adoption, commented Erik Sontheimer, PhD, professor at the RNA Therapeutics Institute at UMass Chan Medical School in an interview with GEN.
To address these challenges, Sontheimer says collaboration with companies that have strong regulatory and commercial experience, in addition to a compatible approach and culture, goes a long way toward supporting long-term clinical success. He noted that synergistic pairings, such as CRISPR Therapeutics and Vertex, and Intellia and Regeneron, largely contributed to the success of Casgevy and the ATTR therapeutic program, respectively.
To support this mission, Danaher and the IGI launched the Danaher-IGI Beacon for CRISPR Cures program in early 2024 to produce a “stacked” manufacturing platform for gene editing therapies with the goal of increasing the number of patients treated with CRISPR-based technology from approximately 210 patients today to many thousands over the next decade.
In this collaboration, Danaher provides manufacturing and technological support to CRISPR therapy researchers within the IGI ecosystem by leveraging its more than 15 diverse businesses, including Integrated DNA Technologies (IDT), Cytiva, Molecular Devices, Leica, Beckman Coulter, and Aldevron.
This vision has translated into impact. Aldevron and IDT were among the crucial team that effectively manufactured KJ’s historic personalized CRISPR gene editing drug, which required a new guide RNA (gRNA) sequence, mRNA-encoded base editor, custom off-target safety services, and clinically validated lipid nanoparticle (LNP) formulation, all on a swift time scale of a few months.
“Our mission in academic science is to create new things and explore new ideas. What we’re not good at is developing ideas so that they can be widely available, affordable, and disseminated,” said Doudna at CRISPR Cures Day, a celebration of the collaboration’s one year anniversary hosted at the IGI in February. “This partnership is our effort to bring those two areas together so that CRISPR can have a global impact.”
While CRISPR is an “electric car in a universe that was built for early model internal combustion engines,” to use Urnov’s words, the promise of gene editing technology remains at the forefront. Time will tell how the power of collaborative minds will push the next wave of CRISPR cures to the clinic.
Read more in World’s First Patient Treated with Personalized CRISPR Therapy and First Personalized CRISPR Gene Editing Therapy Patient Baby KJ Discharged.
The post Advancing CRISPR Cures Requires Cross-Sector Collaboration appeared first on GEN - Genetic Engineering and Biotechnology News.