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 Lysosomal Disorders specialty topic page contains video interviews with key opinion leaders discussing the most relevant FDA actions, clinical guideline updates, and clinical trial findings related to cell therapies, gene therapies, and engineered and regenerative medicines developed for Lysosomal storage diseases. It also houses the most up-to-date clinical news coverage in the field of gene and cell therapy for diseases related to lysosomal storage and dysfunction.

In Episode 5 of ImmunoLogic, Michael T. Lotze, MD, discussed the evolution and future of tumor infiltrating lymphocyte (TIL) therapies.

ImmunoLogic, Episode 5: "Tumor Infiltrating Lymphocytes" With Michael T. Lotze, MD

We're excited to introduce another episode of the 

an assistant professor of microbiology and the director of the Fraietta Lab at the University of Pennsylvania. Fraietta is often joined by cohost 

 a clinical fellow in oncology (MSTR Program) at the University of Pennsylvania. Our hope is that this show will serve as a critical forum for clinicians, translational researchers, and biotech professionals to explore the evolving landscape of immunotherapy. We're seeking to bridge cutting-edge research with practical applications and delve into how immune-based therapies transition from innovative discoveries to transformative patient care solutions

a professor of surgery, immunology, and bioengineering at the University of Pittsburgh, about his work on tumor infiltrating lymphoctye (TIL) therapy. Fraietta and Lotze covered topics including the history of TIL research, the potential of TIL therapy in different tumor types, Lotze and his colleagues' new reciprocal learning model hypothesis, and concluded with some philosophical reflections on cancer research.

 is tailored for an audience fluent in the language of medicine and biotechnology, offering data-driven insights while maintaining accessibility. This podcast is an essential resource for those driving the future of immunotherapy.

Interested in cohosting an episode or being a guest? Have feedback to share? 

If you'd like to get in touch to talk about the show, contact our editorial director, Matt Hoffman: 

Podcasts

In episode 5 of ImmunoLogic, Michael T. Lotze, MD, discusses the evolution and future of tumor-infiltrating lymphocyte therapies.

ImmunoLogic, Episode 5: "Tumor Infiltrators and Triumphs: The Evolution of TIL Therapy" With Michael T. Lotze, MD

In Episode 4 of ImmunoLogic, Caroline Diorio, MD, FRCPC, FAAP, discussed her research on adverse events associated with CAR-T.

 ImmunoLogic, Episode 4: "Inflammatory Storms and Gentle Balances" With Caroline Diorio, MD, FRCPC, FAAP

an assistant professor of microbiology and the director of the Fraietta Lab at the University of Pennsylvania! Fraietta is joined by cohost 

an attending physician at the Cancer Center at Children's Hospital of Philadelphia, about her research into inflammatory toxicities in cell therapy. Diorio, Fraietta, and Minehart covered topics including predicting and managing toxicities like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), the need for rigorous research to understand the underlying biology of these toxicities, the importance of transparency in manufacturing processes, and the potential for decoupling potency from toxicity.

Interested in co-hosting an episode or being a guest? Have feedback to share? 

In Episode 4 of ImmunoLogic, Caroline Diorio, MD, FRCPC, FAAP, discussed her research on adverse events associated with cell therapy.

ImmunoLogic, Episode 4: "Inflammatory Storms and Gentle Balances: Navigating Toxicities in Immunotherapies" With Caroline Diorio, MD, FRCPC, FAAP

In Episode 3 of ImmunoLogic, Marcela Maus, MD, PhD, discussed her research on CAR-T for treating glioblastoma.

ImmunoLogic, Episode 3: "Breaking the Brain’s Barrier: CAR T Cells Take on Glioblastoma" With Marcela Maus, MD, PhD

the director of the Cellular Immunotherapy Program at the Massachusetts General Hospital Cancer Center, about her research into the use of chimeric antigen receptor T-cell (CAR-T) therapy to treat glioblastoma. Maus, Fraietta, and Minehart covered topics including challenges and insights from early clinical trials, innovations and clinical results, antigen expression and the possibility of readministration, as well as the autologous versus allogeneic debate.

ImmunoLogic, Episode 3: "Breaking the Brain’s Barrier: CAR T-Cells Take on Glioblastoma" With Marcela Maus, MD, PhD

In Episode 2 of ImmunoLogic, Bruce Levine, PhD, discussed the current the risk-benefit-ratio for CAR-T therapy.

ImmunoLogic, Episode 2: "Charting New Frontiers in CAR T-Cell Safety" With Bruce Levine, PhD

, a clinical fellow in oncology (MSTR Program) at the University of Pennsylvania. Our hope is that this show will serve as a critical forum for clinicians, translational researchers, and biotech professionals to explore the evolving landscape of immunotherapy. We're seeking to bridge cutting-edge research with practical applications and delve into how immune-based therapies transition from innovative discoveries to transformative patient care solutions

 the Barbara and Edward Netter Professor in Cancer Gene Therapy at the Perelman School of Medicine at the University of Pennsylvania, about the black box warnings for secondary malignancies that were issued by the FDA with regard to the autologous chimeric antigen receptor T-cell (CAR-T) therapies approved by the agency, and the implications of the findings that informed these warnings for the risk-benefit ratio of these therapies. Levine, Fraietta, and Minehart covered topics including risk and informed consent, genetic modification as it relates to safety, epitope spreading and T-cell stimulation, and the importance of the National Institutes of Health (NIH) to CAR T-cell research.

In Episode 1 of ImmunoLogic, Stephen J. Schuster, MD, discussed the potential of treating lymphoma without chemotherapy.

ImmunoLogic, Episode 1: "Chemo-Free Lymphoma? Seriously?" With Stephen J. Schuster, MD

, a clinical fellow in oncology (MSTR Program) at the University of Pennsylvania. Our hope is that this show will become a critical forum for clinicians, translational researchers, and biotech professionals to explore the evolving landscape of immunotherapy. We're seeking to bridge cutting-edge research with practical applications and delve into how immune-based therapies transition from innovative discoveries to transformative patient care solutions

, the director of the Lymphoma Program at Penn Medicine, about the changing role of chemotherapy in lymphoma treatment, and the potential for its elimination. Schuster covered topics including trials for chimeric antigen receptor T-cell (CAR-T) therapy without lymphodepletion, using AI to predict CAR-T treatment outcomes, the importance of T-cell fitness, and the role of persistence in CAR-T success.

Joseph Fraietta, PhD, previews his new podcast, ImmunoLogic

ImmunoLogic Episode 0

an assistant professor of microbiology and the director of the Fraietta Lab at the University of Pennsylvania! Our hope is that this show will become a critical forum for clinicians, translational researchers, and biotech professionals to explore the evolving landscape of immunotherapy. We're seeking to bridge cutting-edge research with practical applications and delve into how immune-based therapies transition from innovative discoveries to transformative patient care solutions.

In this short preview episode, Fraietta outlines the podcast’s mission to scrutinize the critical milestones shaping immunotherapy today and discuss how episodes will analyze the journey from bench to bedside—focusing on the real-world implementation of clinical data and the impact of regulatory achievements on patient outcomes. Topics will include discussions on chimeric antigen receptor (CAR) T-cell therapies, tumor-infiltrating lymphocyte (TIL)-based approaches, antibody-driven treatments, and the latest advances in gene editing technologies such as CRISPR, with a goal of expanding the conversation outside of the field of oncology.

 will be tailored for an audience fluent in the language of medicine and biotechnology, offering data-driven insights while maintaining accessibility. With its first full episode launching in early 2025, this podcast promises to be an essential resource for those driving the future of immunotherapy.

Hosted by Joseph Fraietta, PhD, ImmunoLogic will be tailored for an audience fluent in the language of medicine and biotechnology, offering data-driven insights while maintaining accessibility.

CGTLive® Presents: ImmunoLogic, A Video Podcast With Joseph Fraietta, PhD

Review top news and interview highlights from the week ending August 29, 2025.

CGTLive®’s Weekly Rewind – August 29, 2025

Catch up on the latest news, breakthroughs, and announcements from biotechnology companies making advancements in cell and gene therapies. 

Around the Helix: Cell and Gene Therapy Company Updates – August 27, 2025

The new PDUFA date is set for February 8, 2026.

FDA Bumps Back PDUFA for REGENXBIO's MPS II Gene Therapy RGX-121

The rAAVrh8 gene therapy delivers HEXA and HEXB genes, and has posted postive phase 1/2 results in infantile GM2 gangliosidosis, with enhancements in enzymatic activity and neurological outcomes.

Dual-Vector AAV Gene Therapy for GM2 Gangliosidosis Shows Promising Early Outcomes

Review top news and interview highlights from the week ending August 22, 2025.

CGTLive®’s Weekly Rewind – August 22, 2025

This is the third part of an interview with Kiran Musunuru, MD, PhD and Rebecca Ahrens-Nicklas, MD, PhD. For the first part, 

The physician-scientists at CHOP discussed long-term future expectations for personalized gene editing therapy.

Rebecca Ahrens-Nicklas, MD, PhD, and Kiran Musunuru, MD, PhD, MPH, ML, MRA, on the Implications of the First Successful Personalized Gene Editing Therapy

“It's really moving medicine to be more like surgery in a way—more like a type of procedural healthcare where you're doing one-time interventions that have durable, long-term therapeutic effects. I fully suspect that as this takes off in the coming years—and maybe it'll take more like decades—but we'll eventually get to the point where gene editing will be the standard of care for many diseases, ranging from ultra-rare to the most common diseases. We might get to the point where it's so routine that [it’s similar to] the way we think about antibiotics and blood pressure medications, now. You don't even think twice about it, right?”

A seminal event in the history of gene editing therapy took place recently, with the treatment of a child named KJ with a personalized CRISPR-based gene editing therapy for his severe carbamoyl phosphate synthetase 1 (CPS1) deficiency.

 The treatment, which took place at Children’s Hospital of Philadelphia (CHOP) in the context of an n-of-1 clinical trial in February of this year, was announced publicly by the institution on May 15, 2025, with a press release, a paper in 

the American Society of Gene & Cell Therapy (ASGCT) 28th Annual Meeting

, held May 13 to 17, 2024, in New Orleans, LA.

 spoke with Kiran Musunuru, MD, PhD, a physician-scientist and Barry J. Gertz Professor for translational research in the Perelman School of Medicine at the University of Pennsylvania and CHOP and Rebecca Ahrens-Nicklas, MD, PhD, a physician-scientist and director of the Gene Therapy for Inherited Metabolic Disorders Frontier Program at CHOP, at ASGCT. Following a 

discussion of KJ’s disease and treatment experience

, Musunuru took a broader view and shared his thoughts on how this early step may eventually impact the medical world in the coming years or decades. He posited the idea that gene-editing may eventually become a standard of care for a very wide range of diseases, both rare and common. Afterwards, Ahrens-Nicklas discussed the importance of collaboration in making the plan for KJ’s treatment into a reality and expressed gratitude for the large number of people who played a role in the process.

Click here to view more coverage of the 2025 ASGCT Annual Meeting.

REFERENCES
1. World's first patient treated with personalized CRISPR gene editing therapy at Children’s Hospital of Philadelphia. News release. Children’s Hospital of Philadelphia. May 15, 2025. Accessed May 15, 2025.https://www.chop.edu/news/worlds-first-patient-treated-personalized-crispr-gene-editing-therapy-childrens-hospital
2. Musunuru K, Grandinette SA, Wang X, et al. Patient-specific in vivo gene editing to treat a rare genetic disease. The New England Journal of Medicine. May 15, 2025. Doi: 10.1056/NEJMoa2504747, LA.

Videos

This is the second part of an interview with Kiran Musunuru, MD, PhD and Rebecca Ahrens-Nicklas, MD, PhD. For the first part, 

The physician-scientists at CHOP discussed what lies on the horizon after KJ’s treatment with a CRISPR-based gene editing therapy for CPS1 deficiency.

Rebecca Ahrens-Nicklas, MD, PhD, and Kiran Musunuru, MD, PhD, MPH, ML, MRA, on the Next Steps for Personalized Gene Editing

“I think the long-term goal... is we want this to be a platform that will benefit many patients. We can do n-of-1 studies—we could do them from here to Kingdom Come, but Becca and I are only 2 people and so there's only so much we can do over the lengths of our careers, if we're forecasting over years. We really need something much more scalable that can be applied to help dozens, hundreds, thousands, and eventually, all the people who have rare diseases...”

History was made recently when KJ, an infant with an ultra-rare disease called severe carbamoyl phosphate synthetase 1 (CPS1) deficiency was treated with a personalized CRISPR-based gene editing therapy in an n-of-1 clinical trial carried out at Children’s Hospital of Philadelphia (CHOP).

 In tandem with the announcement of the news by CHOP on May 15, 2025, came a 

 (NEJM) publication on the study and a presentation at 

 got in touch with Kiran Musunuru, MD, PhD, a physician-scientist and Barry J. Gertz Professor for translational research in the Perelman School of Medicine at the University of Pennsylvania and CHOP and Rebecca Ahrens-Nicklas, MD, PhD, a physician-scientist and director of the Gene Therapy for Inherited Metabolic Disorders Frontier Program at CHOP, both of whom were authors on the NEJM paper, to learn more. On the floor of ASGCT, Musunuru and Ahrens-Nicklas discussed the next steps now that several months have passed since KJ received the treatment in February 2025. Ahrens-Nicklas pointed out that KJ will continued to be monitored very closely for safety and efficacy. Looking beyond this, her and Musunuru then discussed the potential future applications of the gene-editing technology used for KJ, emphasizing the ways in which it will need to be adapted to be able to be used at a scale practical for treating a wide range of rare diseases.

REFERENCES
1. World's first patient treated with personalized CRISPR gene editing therapy at Children’s Hospital of Philadelphia. News release. Children’s Hospital of Philadelphia. May 15, 2025. Accessed May 15, 2025.https://www.chop.edu/news/worlds-first-patient-treated-personalized-crispr-gene-editing-therapy-childrens-hospital
2. Musunuru K, Grandinette SA, Wang X, et al. Patient-specific in vivo gene editing to treat a rare genetic disease. 

. Published online May 15, 2025:NEJMoa2504747.

The physician-scientists at CHOP discussed an n-of-1 clinical trial for a CRISPR gene-editing strategy.

Rebecca Ahrens-Nicklas, MD, PhD, and Kiran Musunuru, MD, PhD, MPH, ML, MRA, on Treating CPS1 Deficiency With Personalized Gene Editing

“Something worth emphasizing again is that this was a truly personalized therapy... This drug was made for one patient, this one kid with this very, very, bad urea cycle disorder, and it's tuned to his mutation to correct his mutation. As such, this drug is only for him. It won't actually work for anyone else because nobody else shares that particular mutation. It’s truly n-of-1...”

On May 15, 2025, Children’s Hospital of Philadelphia (CHOP), announced that it had successfully treated a child, named KJ, in an n-of-1 clinical trial for a personalized CRISPR-based gene editing therapy intended to treat KJ’s severe carbamoyl phosphate synthetase 1 (CPS1) deficiency.

 He received the therapy in February 2025 at between 6 and 7 months of age. The child’s case was detailed in newly published paper in 

 entitled “Patient-specific in vivo gene editing to treat a rare genetic disease” and a presentation at 

 sat down with 2 of the paper’s authors, Kiran Musunuru, MD, PhD, a physician-scientist and Barry J. Gertz Professor for translational research in the Perelman School of Medicine at the University of Pennsylvania and CHOP and Rebecca Ahrens-Nicklas, MD, PhD, a physician-scientist and director of the Gene Therapy for Inherited Metabolic Disorders Frontier Program at CHOP, to discuss the news. Ahrens-Nicklas gave some background context about CPS1 deficiency, which is an ultra-rare, life-threatening urea cycle disorder. She explained the devastating nature of the disease, which causes toxic ammonia buildup in newborns, sometimes leading to death within days. The patient in this study had the most severe form, prompting efforts to create a targeted therapy.

Musunuru, drawing on his work in gene editing for cardiovascular disease, noted that the approach used for KJ adapted existing technology to correct the child’s specific genetic mutation. Using a one-time intravenous infusion, the therapy delivered a gene editor to liver cells, aiming to repair the faulty gene. Though still early, Ahrens-Nicklas and Musunuru noted that the child has tolerated the treatment well and shown initial signs of improvement, such as better protein tolerance. They emphasized that this is a single-patient case, so broader conclusions are premature, but the early success in safety and early efficacy indicators offer hope for expanding personalized gene therapies in the future.

Rebecca Ahrens-Nicklas, MD, PhD; and Kiran Musunuru, MD, PhD, MPH, ML, MRA, on Treating CPS1 Deficiency With Personalized Gene Editing

This is the second part of an interview with Reena Sharma, MD. For the first part,

The adult metabolic consultant at Salford Royal Hospital discussed areas of interest for future study for the Gaucher disease gene therapy product.

Reena Sharma, MD, on Future Plans for Evaluating FLT201

“When you think about patients with disease like Pompe or even Fabry, their unmet needs with the current therapy are huge. So we may think that, ‘Oh, [patients with diseases like Gaucher disease] are okay,’ but I think what we misunderstand and probably do not realize is that although their issues may not be as big as some of the other conditions we look after, they still mean a lot to this cohort of patients. They still have burden of therapy, which is a lifelong therapy, they still have unmet needs, their bone complications are ongoing, so I don't think as clinicians, we should underestimate how it's impacting the patients, and we should always look at better therapies and explore better options...”

Spur Therapeutics’FLT201, an adeno-associated virus (AAV) vector-based gene therapy intended to serve as a one-time treatment option for Gaucher disease, is currently being assessed in the phase 1/2 GALILEO-1 clinical trial (NCT05324943). Interim results from this study were recently presented by Reena Sharma, MD, an adult metabolic consultant at Salford Royal Hospital, at 

, held February 3 to 7, 2025, in San Diego, California.

 interviewed Sharma during the conference to learn more. After going over 

, Sharma discussed some of the future plans for the therapy, emphasizing the need to explore biochemical parameters and disease burden in the bones, areas of interest which were not touched on in the presentation at the meeting. She also pointed out that future studies should also evaluate the therapy's impact on patients' quality of life, pain levels, and overall well-being. Additionally, Sharma noted that further exploration of antibody responses is necessary. In the small cohort treated with FLT201, 2 patients developed transient antibodies. Although it did not appear to affect clinical efficacy, she noted that long-term effects should be monitored. Sharma also spoke about the need for clinicians to reconsider how they think about the unmet needs for patient communities in general and stated that she is looking forward to the phase 3 trial for FLT201.

REFERENCES
1. Sharma R, Goker-Alpan O, Schwartz I, Giraldo P, Ferrante F, Foulds P. Results from GALILEO-1, a first-in-human clinical trial of FLT201 AAV gene therapy in adult patients with Gaucher Disease Type 1. Presented at: WORLD

, held February 3-7, 2025, in San Diego, California. Poster #318

The adult metabolic consultant at Salford Royal Hospital discussed areas of interest for future study for the Gaucher disease gene therapy product. 

The adult metabolic consultant at Salford Royal Hospital discussed results she presented at the 21st Annual WORLDSymposium.

Reena Sharma, MD, on Assessing Spur Therapeutics’ Gene Therapy FLT201 in Gaucher Disease

“It certainly offers a very promising result and makes a case for exploring further as a treatment for this group of patients in the future, which can not only stabilize the condition, but also actually take away some of the disease burden that has not been managed by the current therapy.”

Currently, standard of care (SOC) treatment options for Gaucher disease include enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). Although these options can provide a meaningful clinical benefit, they have a substantial burden of care, as they must be regularly administered to patients throughout their lifetime. In order to address this unmet need, Spur Therapeutics is currently developing FLT201, an adeno-associated virus (AAV) vector-based gene therapy, with the intention of providing a one-time treatment option for Gaucher disease. The therapy is currently being evaluated in the phase 1/2 GALILEO-1 clinical trial (NCT05324943). Interim results from this study were recently presented in a poster at 

 reached out to Reena Sharma, MD, an adult metabolic consultant at Salford Royal Hospital, who presented the data at WORLD

, to learn more. Sharma explained what FLT201 is and how it functions, and then went over the key results that were presented and their implications. She noted that the gene therapy uses an AAVS3 capsid designed for efficient liver uptake and delivers a transgene encoding an engineered enzyme (GCase85), which is designed to be longer-acting than the natural GCase enzyme that is found at deficient levels in patients with Gaucher disease.

 Sharma highlighted that all 5 patients included in the efficacy analysis presented showed expression of GCase85 and that 4 of these 5 patients were able to come off of their SOC therapy within 4 to 11 weeks of treatment with FLT201.

, held February 3-7, 2025, in San Diego, California. Poster #318
2. Spur Therapeutics announces positive data from phase 1/2 GALILEO-1 trial of FLT201, its gene therapy candidate for Gaucher disease, at WORLD

. News release. Spur Therapeutics. February 4, 2025. Accessed February 4, 2025. https://www.globenewswire.com/news-release/2025/02/04/3020229/0/en/Spur-Therapeutics-Announces-Positive-Data-from-Phase-1-2-GALILEO-1-Trial-of-FLT201-Its-Gene-Therapy-Candidate-for-Gaucher-Disease-at-WORLDSymposium.html

The chief medical officer at Creyon Bio discussed future applications for the company’s AI-guided discovery platform. 

David Dimmock, MBBS, on Accelerating Therapy Discovery and Approval With AI 

“The FDA has approved a drug based on 4 patients... So, we believe it is possible, even with very small patient populations to get drugs approved, but to get drugs approved, you need to do all the appropriate studies, which means you need to walk into the studies with a drug with a very high prior probability of success. So having the platform in place enables us to walk in with very high expectations that our drug is going to be safe.”

Creyon Bio has demonstrated proof-of-concept of its AI discovery platform to develop an antisense oligonucleotide (ASO) therapeutic in a case study of a single patient with a de novo heterozygous pathogenic variant causing a missense change in TNPO2. The AI model informed the target and the produced ASO knocked down an allele selective toxic Transportin-2 (TNPO2) protein. The patient was dosed within 1 year of initiating the project with up to 3 doses of up to 40 mg.

Investigators found that multiple doses of the ASO was well-tolerated in the treated child. The child has received 3 doses so far and investigators are anticipating the next dose, as between doses, clinical benefit would wear off and improvements would regress, demonstrating a need to redose with the ASO. After each dose, the child experienced a dramatic clinical benefit, with reductions in seizure frequency subsequent to the second dose and regained developmental milestones. The child also developed new skills following the third dose.

® spoke with David Dimmock, MBBS, chief medical officer at Creyon, to learn more about the AI-guided platform and potential future applications of it. He also discussed future plans for the company and its ambitions for its ASO platform.

Dimmock DP, Bird L, Bouck A, et al. AI Enabled ASO Design Can Lead to Rapid Initiation of Treatment for an Ultra-Rare Disorder Leading to Allele Selective Knockdown of a Toxic Protein and Consequent Clinical Improvement. Presented at: ASGCT 27th Annual Meeting, May 7-10; Baltimore, Maryland. Abstract #309

The chief medical officer at Creyon Bio discussed findings from a treated patient with a TNP02 missense mutation. 

David Dimmock, MBBS, on a Promising Case Study of Ultra-Rare, AI-Guided, ASO Development 

“We’re at the point now, we're very confident that the drug is working, because every time we give the drug, the child gets dramatically better, but unfortunately, it seems to be wearing off, and so we're in the process of working out what safety data we need to persuade everybody that it would be more appropriate to dose this child more frequently.”

An antisense oligonucleotide (ASO) therapeutic demonstrated proof-of-concept for Creyon Bio’s AI discovery platform in a case study of a single patient with a de novo heterozygous pathogenic variant causing a missense change in TNPO2. The produced ASO knocked down an allele selective toxic Transportin-2 (TNPO2) protein, the target of which was informed using Creyon'd AI model. The patient was dosed within 1 year of initiating the project with up to 3 doses of up to 40 mg.

The child experienced a dramatic clinical benefit, with reductions in seizure frequency subsequent to the second dose and regained developmental milestones. The child also developed new skills following the third dose. Between doses, clinical benefit would wear off and improvements would regress, demonstrating a need to redose with the ASO. The child has received 3 doses so far and investigators are anticipating the next dose.

 spoke with David Dimmock, MBBS, chief medical officer at Creyon, to learn more about how the case study. He overviewed the disease pathology of the patient with the TNP02 missense mutation and the treatment course so far. He detailed the findings from the case study and the milestones that the child has received. He explained that definitive benefits have been observed with the ASO but the need to redose to maintain these benefits has also established.

The chief medical officer and head of translational research at Ring Therapeutics discussed research presented at ASGCT 2024. 

Chris Wright, MD, PhD, on Annelloviruses, a Potential Alternative to AAV for Gene Therapy 

“We were looking in the body for different viruses that are persisting there, but not causing any problems. So, we did find a number of viruses, the anelloviruses. Anelloviruses actually make up about 80% of all the viruses in a person's body. And it turns out that that they've been there throughout all of the person's life, pretty much shortly after birth. So, they persist for a long period of time, and they don't appear to cause any problems, they don't induce an immune reaction, and they don't seem to have any associations with diseases. So, we thought that could be a great virus to use to try to deliver gene therapy, because it should be a safe approach.”

Ring Therapeutics is developing anellovectors as potential alternatives to adeno-associated virus (AAV) gene therapies. AAV therapies, although currently the standard for gene therapies and an approved modality, have inherent challenges, including immune responses and lack of redosability. Anelloviruses, found naturally in the human body, have potential to address these challenges for gene therapies.

Ring presented data from multiple studies on anelloviruses at 

the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting

, held May 7 to 10, 2024, in Baltimore, Maryland. 

spoke with Chris Wright, MD, PhD, chief medical officer and head, translational research, Ring Therapeutics, to learn more about anelloviruses and the data presented at ASGCT. He overviewed the outstanding issues with AAV therapies and how anelloviruses may address these challenges. He also outlined the different research presented at the meeting, including demonstrating a large payload with anelloviruses, demonstrating transduction in the eye in nonhuman primates, and demonstrating redosability without issue.

Bounoutas GS, Pozsgai R, Gold I, et al. Anellovectors, a Gene Delivery Platform Based on Commensal Human Anelloviruses, Have the Potential to Evade the Immune System and Deliver DNA Payloads to a Broad Range of Tissues in a Redosable Manner. Presented at: ASGCT 27th Annual Meeting, May 7-10; Baltimore, Maryland. Abstract #203

Chris Wright, MD, PhD, on Anelloviruses, a Potential Alternative to AAV for Gene Therapy 

The Don and Marilyn Anderson Professor of Oncology at University of Wisconsin – Madison discuss the state of cell and gene therapy development. 

Jacques Galipeau, MD, on Exponential Progress With Cell and Gene Therapy 

"Ten years ago, we were starting clinical trials. There was really no meaningful number of approved cell therapies in international jurisdictions. Fast forward a decade, now we have at least 6 key products that are approved, gene engineered stem cells have been approved. TILs have been approved, and the regulators are telling us that they anticipate that the number of approvals is going to grow every year. So now we have approved therapies and it’s not theoretical, and that's expanding. And there's this whole pipeline behind it.”

Jacques Galipeau, MD, Don and Marilyn Anderson Professor of Oncology at University of Wisconsin – Madison, and president, International Society for Cell and Gene Therapy (ISCT), chaired the presidential plenary of this year’s meeting, held in Vancouver, Canada, from May 29 - June 1. The plenary brought together leaders of sister scholarly societies to discuss cell and gene therapy development including Anna Sureda, MD, PhD, president of European Society for Blood and Marrow Transplantation; Amander Clark, PhD, president, International Society for Stem Cell Research; and Corey Cutler, MD, MPH, FRCP(C), president, American Society for Transplantation and Cellular Therapy. The speakers discussed challenges with cell and gene therapies and their current state of development, within each country and internationally.

® spoke with Galipeau to learn morethe state of gene and cell therapy investigations and development. He emphasized the progress in the field over the last 10 years, and how the number of novel approvals is expected to keep growing. Accordingly, he noted that the ISCT meeting is growing in attendance every year, and this year’s meeting, which was the 30th anniversary meeting, broke the record for attendance so far.

Galipeau J, Sureda A, Clark A, Cutler C. La présidentielle. Presented at: ISCT 2024 Meeting, held in Vancouver, Canada, from May 29 – June 1.

The Don and Marilyn Anderson Professor of Oncology at University of Wisconsin – Madison discussed the state of cell and gene therapy development. 

The chief medical officer at Creyon Bio overviewed the development of an allele-selective TNPO2 protein for a single patient with a de novo pathology. 

David Dimmock, MBBS, on AI-Guided ASO Development for Ultra-Rare Diseases 

“The hope was could we actually design an oligo that could get rid of this bad protein that was building up in the brain whilst leaving the good copy of that gene alone? And would that actually make a difference? The challenge with this disease is we knew the genetic changes that were causing the disease [but] at this point we didn't have any long read sequencing, so we didn't know of any other parts of the genome that were on the bad copy of the gene. So, we were forced to design the oligo to actually hit the disease-causing variant.”

An antisense oligonucleotide (ASO) therapeutic demonstrated knocking down an allele selective toxic Transportin-2 (TNPO2) protein, the target of which was informed using an artificial intelligence (AI) model, in a case study of a single patient with a de novo heterozygous pathogenic variant causing a missense change in TNPO2.

The ASO was developed by Creyon Bio with the use of the company’s AI discovery platform. The path to treatment was a fast one, with the patient dosed within 1 year of initiating the project. The child tolerated dose escalation up to 40mg with up to 3 doses.

Investigators found that the child had a dramatic reduction in seizure frequency subsequent to the second dose and regained developmental milestones that were lost and developed new skills following the third dose. These improvements regressed and were regained between and after doses.

spoke with David Dimmock, MBBS, chief medical officer at Creyon, to learn more about how the ASO was developed for this case study and challenges specific to it that the development faced.

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