Some AAV manufacturing processes use adherent cells grown in stacked trays. AGTC sees that model as a barrier to scaling, pointing to the inability to scale processes up by adding volume. Scaling of adherent cell processes requires additional surface area.
AGTC overcame that limitation by designing a process that makes use of bioreactors, enabling it to scale up from 50 L to 500 L and beyond without significantly increasing its footprint. AGTC enhanced the approach with changes it says improved yield by more than 10 fold.
We adjusted the upstream process which uses two HSV helper viruses to increase AAV production in a number of ways, one of which was optimizing the ratio and amount of the two viruses. Further, we optimized the bioreactor conditions to increase cell density. Both of these changes led to substantial increases in volumetric productivity, said AGTC CEO Sue Washer.
Adjusting the ratios and conditions of the process enabled AGTC to make more vectors and increase the percentage of them that are full. AGTC is now achieving finished product specifications that demonstrate nearly 90% full capsids.
Washer went on to say that AGTC also optimized the column chromatography purification process to more completely separate residuals from vectors. In doing so, AGTC was able to collect a higher quality product from the elution peak, according to Washer.
Using the process, AGTC estimates it could generate 2,000 ophthalmology gene therapy doses from a 50-L manufacturing run. That would enable AGTC to support its move into late-phase clinical trials using a relatively small manufacturing footprint.
The improvements could prove particularly valuable to AGTC as it expands beyond diseases affecting the eye. The gene therapy doses needed to treat ocular diseases are far smaller than those required to address conditions affecting other organs, which typically need to be given systemically.
The industry-wide move from rare diseases treated via local delivery to more common conditions that require systemic administration is putting a strain on manufacturing capacity. If AGTC is right, its process will equip it to manage the manufacturing side of the shift in therapeutic focus better than some other gene therapy companies.
AGTC is now advancing programs that will enable it to start putting that hypothesis to the test. While AGTCs clinical pipeline is focused on rare genetic eye diseases, the biotech is working to get gene therapies for central nervous system disorders into human testing. Washer is alert to the implications of AGTCs manufacturing process.
Improved yields makes use of gene therapy for larger patient populations or systemic diseases much more achievable, said Washer.
AGTC is working to further improve the system. Ongoing areas of activity relate to purification, where Washer sees opportunities to eliminate all process residuals, and the improvement of yields and the percentage of full capsids.
The nature of the process means manufacturing runs could become more productive even in the absence of further technological advances. Simply running the same process at a larger scale should confer some benefits.
Continuing to scale to larger bioreactors could continue to increase the number of doses from a single run and drive down costs as bioreactor scale-up does not put a burden on factory space or FTE needed like the use of plastic flat-stock does, said Washer.
Read the rest here:
Using HSV helper viruses to increase AAV production - BioPharma-Reporter.com
- Krystal Biotech Inc (KRYS) Reports Strong Q4 and Full Year 2023 Financial Results - Yahoo Finance - February 27th, 2024
- New sickle cell gene therapies are a breakthrough, but solving how to pay their high prices is a struggle - CNBC - February 27th, 2024
- 10 gene therapy companies you should know about - Labiotech.eu - February 27th, 2024
- Former Penn employee sues Gene Therapy Program director, alleging 'unethical and illegal conduct' - The Daily Pennsylvanian - February 27th, 2024
- Gene therapy can't cure deafness because it doesn't need to be cured - The Philadelphia Inquirer - February 27th, 2024
- Fetal surgery expert Tippi MacKenzie shifts to in-utero gene therapy - STAT - February 27th, 2024
- Therapeutic Solutions International Files Patent on Facilitating Effects of JadiCells on Gene Therapy Mediated Cell ... - Business Wire - February 27th, 2024
- CU Anschutz Set to Launch Gene Therapy Trials for Heart Disorder - University of Colorado Anschutz Medical Campus - February 27th, 2024
- ICH targets cell and gene therapies, real-world data as topics ripe for harmonization - Regulatory Focus - February 27th, 2024
- Encoded Therapeutics Announces UK CTA Approval for Dravet Syndrome Gene Therapy Candidate ETX101 - Business Wire - February 27th, 2024
- Voyager Therapeutics Announces Selection of Gene Therapy Development Candidate for Friedreich's Ataxia in ... - GlobeNewswire - February 27th, 2024
- Therapeutic Solutions International Files Patent on Facilitating Effects of JadiCells on Gene Therapy Mediated Cell ... - The Bakersfield Californian - February 27th, 2024
- Ring Therapeutics, a Flagship gene therapy startup, lays off 20% of staff - STAT - February 27th, 2024
- Ed Silverman on new gene therapies, biosimilars, coffee, and more - STAT - STAT - February 27th, 2024
- Combatting HIV using gene therapy - Drug Target Review - February 27th, 2024
- NCDHHS working with federal government on increasing access to sickle cell disease treatment - WECT - February 27th, 2024
- Cell Therapy Weekly: FDA Approves First Cell Therapy For Solid Tumors - RegMedNet - February 27th, 2024
- Rejuvenate Bio Announces Gene Therapy-Mediated Partial Reprogramming Extends Lifespan and Reverses Age ... - Business Wire - February 27th, 2024
- New sickle cell therapy uses gene editing at MUSC | Health | postandcourier.com - The Post and Courier - February 27th, 2024
- Long-term and real-world safety and efficacy of retroviral gene therapy for adenosine deaminase deficiency - Nature.com - February 18th, 2024
- Gene therapy, blood transfusions, stool monitoring: The Sydneysiders trying to escape death - Sydney Morning Herald - February 18th, 2024
- Not too late to repair: gene therapy improves advanced heart failure in animal model - Baylor College of Medicine | BCM - February 18th, 2024
- Direct Administration of CRISPR-Cas9: Tools for Cell and Gene Therapy - Forbes - February 18th, 2024
- Gene therapy's promise seen in its success for AADC deficiency - AADC News - February 18th, 2024
- First Patient Randomized in AskBio Phase II Gene Therapy Trial for Congestive Heart Failure Treatment - Diagnostic and Interventional Cardiology - February 18th, 2024
- FDA to review expanded use of Sarepta Duchenne gene therapy - Yahoo Finance - February 18th, 2024
- How gene therapy can help treat a rare blood disorder - KUTV 2News - February 18th, 2024
- CRISPR gene therapy Casgevy secures approval in Europe - Pharmaceutical Technology - February 18th, 2024
- FDA Updates for the Week of Feb. 12, 2024: New Approvals, an Extended Review and Goal Dates Set - Managed Healthcare Executive - February 18th, 2024
- First Patient Randomized in AskBio Phase II Gene Therapy Trial for Congestive Heart Failure - Business Wire - February 18th, 2024
- Lisa Jarvis: A cure for some kinds of hearing loss? Gene therapies are getting closer - St. Paul Pioneer Press - February 18th, 2024
- Spinal Muscular Atrophy Market: Navigating Therapeutic Advances towards USD 5.6 Billion by 2034, with a CAGR of ... - Yahoo Finance - February 18th, 2024
- Crispr Therapeutics' Gene Therapy Wins EU Approval - TipRanks.com - TipRanks - February 18th, 2024
- Revolutionizing Gene Therapy: A Novel Technique for In Vivo CAR T Cells - Medriva - February 18th, 2024
- How Stella Vnook is 'infusing innovation' into cell therapies with Likarda's technology - BioPharma-Reporter.com - February 18th, 2024
- Using cancer's 'superpower' to boost T-cell therapies in mice - FierceBiotech - February 18th, 2024
- Parkinson's Disease Patient Identification and Education Will Need to Improve When New Disease Modifying ... - Yahoo Finance - February 18th, 2024
- CRISPR (CRSP) to Report Q4 Earnings: What's in the Cards? - Yahoo Finance - February 18th, 2024
- Gene Therapy: A Ray of Hope for Heart Failure Treatment | Health News - Medriva - February 18th, 2024
- Gene therapy trials restore hearing to children born deaf - The Hill - February 2nd, 2024
- Early Trial Success for Inherited Deafness Gene-Therapy - RegMedNet - February 2nd, 2024
- Sickle cell gene therapy first focus of Medicaid pay model - Modern Healthcare - February 2nd, 2024
- Beyond chemotherapy: Navigating the promise and perils of CAR-T therapy in pediatric cancer - BioPharma-Reporter.com - February 2nd, 2024
- Angiodema: Gene therapy blocks painful hereditary disorder - BBC - February 2nd, 2024
- FDA: Genome editing therapies may use accelerated approval pathway - Regulatory Focus - February 2nd, 2024
- CRISPR tech treats severe hereditary condition successfully - Interesting Engineering - February 2nd, 2024
- Gene Therapy Restores Hearing in Small Trial for Kids With Hereditary Deafness - Technology Networks - February 2nd, 2024
- Gene-based therapy may slow development of life-threatening heart condition - Medical Xpress - February 2nd, 2024
- Jaguar Gene Therapy Announces FDA Clearance of IND to Study JAG201 in a Genetic Form of Autism Spectrum ... - Business Wire - February 2nd, 2024
- Replacing the PKP2 gene prolongs survival in ARVC patients - Drug Target Review - February 2nd, 2024
- Cell and gene therapies top pharmaceutical industry trend to watch for 2024 - Pharmaceutical Technology - February 2nd, 2024
- Gene Therapy Restores Hearing in Children with Hereditary Deafness - The Hearing Review - February 2nd, 2024
- 2 Dutch among 10 "functionally cured" of hereditary swelling disease by new gene therapy - NL Times - February 2nd, 2024
- FDA publishes final industry guidance for CAR-T and gene therapies - PMLiVE - February 2nd, 2024
- Gene therapy cures hereditary deafness in two people - Advanced Science News - February 2nd, 2024
- Hearing Restored in Deaf Children in Gene Therapy Clinical Trial - Securities.io - February 2nd, 2024
- Vivet Therapeutics Receive 4.9 Million to Advance Development of Gene Therapy - European Pharmaceutical Manufacturer - February 2nd, 2024
- Adverum Biotechnologies will Host Webcast to Review LUNA Phase 2 Preliminary Efficacy and Safety Results on ... - GlobeNewswire - February 2nd, 2024
- Allogene parks Notch CARs, leaving one on the road - FierceBiotech - February 2nd, 2024
- Experimental gene therapy allows kids with inherited deafness to hear - The Associated Press - January 25th, 2024
- Gene-therapy breakthrough allows congenitally deaf children to hear Harvard Gazette - Harvard Gazette - January 25th, 2024
- Gene therapies restore hearing in several kids with inherited deafness - Livescience.com - January 25th, 2024
- Boy born deaf can hear for the first time thanks to a gene therapy procedure - NBC 6 South Florida - January 25th, 2024
- Gene therapy restores hearing in children with hereditary deafness - Medical Xpress - January 25th, 2024
- Children's Hospital of Philadelphia Performs First in U.S. Gene Therapy Procedure to Treat Genetic Hearing Loss - PR Newswire - January 25th, 2024
- Children's Hospital of Philadelphia uses gene therapy to help 11-year-old boy hear for 1st time - WPVI-TV - January 25th, 2024
- Breakthrough gene therapy treatment restores hearing in children born deaf - The Independent - January 25th, 2024
- Gene Therapy Administered Via Virus Cures Deafness in 11-Year-Old Boy - Futurism - January 25th, 2024
- 11-Year-Old Boy Hears For First Time Ever Thanks To Gene Therapy Breakthrough - IFLScience - January 25th, 2024
- Gene Therapy Deafness | National | caledonianrecord.com - The Caledonian-Record - January 25th, 2024
- Sickle cell gene therapy to be covered by Blue Cross insurers - Modern Healthcare - January 25th, 2024
- Experimental gene therapy allows kids with inherited deafness to hear - Jackson Hole News&Guide - January 25th, 2024
- Gene therapy allows 11-year-old boy to hear for the first time - Latest From ITV News - ITVX - January 25th, 2024
- Experimental Gene Therapy Allows Kids With Inherited Deafness To Hear - Southern Minnesota News - January 25th, 2024
- Joint US-China gene therapy trials restore hearing in 5 kids, a first - Interesting Engineering - January 25th, 2024
- Gene Therapy Deafness | Nation | The Daily News - Galveston County Daily News - January 25th, 2024
- In Draft Guidance for Cell and Gene Therapy Industry, FDA Broadens its Approach to Product Potency - Precision Medicine Online - January 25th, 2024
- Gene therapy helps restore hearing in children with hereditary deafness - Shropshire Star - January 25th, 2024
- Gene therapy breakthrough enables deaf boy to hear for the first time - The Week - January 25th, 2024
- FDA eyes collaborative review pilot for gene therapies - Regulatory Focus - January 17th, 2024