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Solutions for Lentivirus Manufacturing

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Lentivirus is an efficient gene delivery vector because of its high-efficiency infection of dividing and non-dividing cells, low immunogenicity and long-term stable expression of a transgene. Examples of lentiviruses are HIV, SIV, and FIV.

Repligen solutions for Lentivirus manufacturing

Needs and challenges:

  • Tools and processes are needed that take into consideration the shear/pH/temperature sensitivity of Lentivirus.
  • Closed and aseptic processing is ideal; a sterile flow path is key to application.
  • Full or partial media exchange may be needed for optimized viral genome titer.

Repligen solutions can help overcome obstacles in Lentivirus bioprocessing.

Click on the unit operation below to find productivity and throughput solutions you can implement today. 

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XCell ATF® 
Systems

Scalable, single-use cell retention device for cell culture process intensification and media exchange

Higher pre-transfection viable cell density and total capsid titer

 

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XCell ATF® 
Systems

ProConnex® 
Flow Paths

Spectrum® Hollow
Fiber Filters

KrosFlo® TFF
Systems

Scalable, single-use cell retention device for cell culture process intensification and media exchange

Higher pre-transfection viable cell density and total capsid titer

Sterile, disposable, sensor-integrated and ready-to-operate

Compatible with hollow fiber and flat sheet filters

Ideal for Gene Therapy: aseptic processing, reduced cross-contamination risk

Wide range of formats, chemistries and pore sizes

Ideal for UF/DF of large, shear-sensitive molecules, like Lentivirus - high yield and improved impurity removal in process and/or final purified product formulation

Fully automated, easy to operate

Scalable from bench to production

Compatible with hollow fiber and flat sheet TFF

Low hold-up volumes

 

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XCell ATF®
 Systems

ProConnex® 
Flow Paths

Spectrum® Hollow
Fiber Filters

KrosFlo® TFF
Systems

SoloVPE®
Device

OPUS® 
Columns

Scalable, single-use cell retention device for cell culture process intensification and media exchange

Higher pre-transfection viable cell density and total capsid titer

Sterile, disposable, sensor-integrated and ready-to-operate

Compatible with hollow fiber and flat sheet filters

Ideal for Gene Therapy: aseptic processing, reduced cross-contamination risk

Wide range of formats, chemistries and pore sizes

Ideal for UF/DF of large, shear-sensitive molecules, like Lentivirus - high yield and improved impurity removal in process and/or final purified product formulation

Fully automated, easy to operate

Scalable from bench to production

Compatible with hollow fiber and flat sheet TFF

Low hold-up volumes

Rapid and accurate absorbance measurements; Avoid labor-intensive, precision-impacting sample dilution

Automated plasmid/viral vector concentration measurement with increased accuracy and repeatability

Ready-to-use, no packing expertise needed

Pack any resin for AAV, Lentivirus, or plasmid purification (including custom resins)

0.5 - 30 cm IDs | 5 - 30 cm bed heights

KrosFlo-TFDF-Lab-System
KrosFlo® TFDF®
Systems

Closed, single-use, automated, alternative to centrifugation and primary depth filtration

Ideal for Lentivirus processes: Improved yields low shear, low hold-up volumes

Scalable from 1 to 2000L

KrosFlo_Pro-Connex.jpg hf_pardot.jpg KrosFlo-tff-systems.jpg SOLO2_1.jpg

ProConnex® 
Flow Paths

Spectrum® Hollow
Fiber Filters

KrosFlo® TFF
Systems

SoloVPE®
Device

Sterile, disposable, sensor-integrated and ready-to-operate

Compatible with hollow fiber and flat sheet filters

Ideal for Gene Therapy: aseptic processing, reduced cross-contamination risk

Wide range of formats, chemistries and pore sizes

Ideal for UF/DF of large, shear-sensitive molecules, like Lentivirus - high yield and improved impurity removal in process and/or final purified product formulation

Fully automated, easy to operate

Scalable from bench to production

Compatible with hollow fiber and flat sheet TFF

Low hold-up volumes

Rapid and accurate absorbance measurements; Avoid labor-intensive, precision-impacting sample dilution

Automated plasmid/viral vector concentration measurement with increased accuracy and repeatability

opus_GT.jpg SOLO2_1.jpg

OPUS® 
Columns

SoloVPE®
Device

Ready-to-use, no packing expertise needed

Pack any resin for AAV, Lentivirus, or plasmid purification (including custom resins)

0.5 - 30 cm IDs | 5 - 30 cm bed heights

Rapid and accurate absorbance measurements; Avoid labor-intensive, precision-impacting sample dilution

Automated plasmid/viral vector concentration measurement with increased accuracy and repeatability

KrosFlo_Pro-Connex.jpg hf_pardot.jpg KrosFlo-tff-systems.jpg SOLO2_1.jpg

ProConnex® 
Flow Paths

Spectrum® Hollow
Fiber Filters

KrosFlo® TFF
Systems

SoloVPE®
Device

Sterile, disposable, sensor-integrated and ready-to-operate

Compatible with hollow fiber and flat sheet filters

Ideal for Gene Therapy: aseptic processing, reduced cross-contamination risk

Wide range of formats, chemistries and pore sizes

Ideal for UF/DF of large, shear-sensitive molecules, like Lentivirus - high yield and improved impurity removal in process and/or final purified product formulation

Fully automated, easy to operate

Scalable from bench to production

Compatible with hollow fiber and flat sheet TFF

Low hold-up volumes

Rapid and accurate absorbance measurements; Avoid labor-intensive, precision-impacting sample dilution

Automated plasmid/viral vector concentration measurement with increased accuracy and repeatability

SOLO2_1.jpg
SoloVPE®
Device

Rapid and accurate absorbance measurements; Avoid labor-intensive, precision-impacting sample dilution

Automated plasmid/viral vector concentration measurement with increased accuracy and repeatability

Lentiviral process intensification yields 2.5X harvest

Lentiviral process intensification achieves a 250% overall lentiviral harvest yield increase over depth filtration. After first harvest, the process generates >90% lentiviral yield compared to 70% using depth filtration. Low shear TFDF® technology preserves HEK293 cell growth and enables a second harvest that results in 80% more yield. Process flux maintained at 750 LMH throughout without fouling. Transmembrane pressure maintained less than 3 psi across both harvests with one filter. 

Higher product yield and transmission with HPH 

  • >90% lentivirus transmission with HPH using TFDF® 
  • 30% higher yield with first TFDF® harvest compared to depth filtration 
  • Low shear of TFDF® preserves suspension HEK293 cells and enables a second harvest 

Source: Cell & Gene Therapy Insights, 2000, 6, 455-467  

Multiple harvests with the same filter while maintaining low TMP  

  • 2.5X yield increase over depth filtration  
  • TMP < 3psi after two harvests with the same TFDF® filter  
  • Clarified product eliminates centrifugation step and reduces depth filtration requirement  

Repligen solutions from gene to therapy

Gene Therapy has immense potential to transform the lives of patients with genetic diseases. As demand for plasmids and viral vectors outpace capacity, a greater than 10-fold and potentially close to 100-fold increase in manufacturing efficiency for the gene therapy reagents is likely required to meet a demand curve that is increasing exponentially.  Repligen solutions aim to meet the needs for optimized processes, higher yields, and improved process quality - setting new standards for modern scalable processes from gene to therapy.

Virtual seminar | Gene Therapy manufacturing 2.0

REPLIGEN technical support ENSUres Success

Repligen Field Application Specialists (FAS) with expertise in Gene Therapy provide support from consultation to implementation globally. 

Consultation

  • Theory
  • Technology fit
  • Experimental plan

Evaluation

  • Demonstration
  • Training
  • Data analysis

Development

  • Optimization
  • Flow Path sizing
  • System sizing

Implementation

  • Scale-up
  • Validation
  • Long-term training plan

Resources

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Lentiviral vector manufacturing process enchancement utilizing TFDF™ technology
by Thomas Williams, Oliver Goodyear, Lee Davies, Carol Knevelman, Michael Bransby, Kyriacos Mitrophanous and James Miskin
Cell and Gene Therapy Insights, April 2020

 

AAV Studies Deploying a Closed, Irradiated, Single-use Flat Sheet TFF Device
by David Bianchi, Carl Breuning, Michael LaBreck, Shelly Parra, Mary Jo Wojtusik, Repligen Corporation 
Alex Meola, Michael Mercaldi, Thomas Thiers, Homology, Medicines Inc. 

Repligen Corporation
Homology, Medicines Inc.
July 2020