Challenges of up-scaling lentivirus production and processing

McCarron, Alexandra; Donnelley, Martin; McIntyre, Chantelle; Parsons, David

doi:10.1016/j.jbiotec.2016.10.016

Cited by 88 publications

(86 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, using approvals of clinical applications of viral vectors for comparison, we will find this is not true. Viral vectors are inherently complicated made of viral proteins, which are immuonogenic and multifunctional and can change their structures responding to in vivo environments, not to mention their production complications and difficulties . However, because of their high efficiencies and therapeutic efficacies, viral vectors have been under extensive clinical trials for various diseases including cancer and now one is in clinical use in Europe .…”

Section: Future Directions For Effective Nanomedicine Designmentioning

confidence: 99%

Rational Design of Cancer Nanomedicine: Nanoproperty Integration and Synchronization

et al. 2017

View full text Add to dashboard Cite

Current cancer nanomedicines can only mitigate adverse effects but fail to enhance therapeutic efficacies of anticancer drugs. Rational design of next-generation cancer nanomedicines should aim to enhance their therapeutic efficacies. Taking this into account, this review first analyzes the typical cancer-drug-delivery process of an intravenously administered nanomedicine and concludes that the delivery involves a five-step CAPIR cascade and that high efficiency at every step is critical to guarantee high overall therapeutic efficiency. Further analysis shows that the nanoproperties needed in each step for a nanomedicine to maximize its efficiency are different and even opposing in different steps, particularly what the authors call the PEG, surface-charge, size and stability dilemmas. To resolve those dilemmas in order to integrate all needed nanoproperties into one nanomedicine, stability, surface and size nanoproperty transitions (3S transitions for short) are proposed and the reported strategies to realize these transitions are comprehensively summarized. Examples of nanomedicines capable of the 3S transitions are discussed, as are future research directions to design high-performance cancer nanomedicines and their clinical translations.

show abstract

Section: Future Directions For Effective Nanomedicine Designmentioning

confidence: 99%

Rational Design of Cancer Nanomedicine: Nanoproperty Integration and Synchronization

et al. 2017

View full text Add to dashboard Cite

show abstract

“…To facilitate the translational success emerging with in-vivo gene transfer, considerable focus must be brought to bear on the cost-of-goods associated with manufacturing vectors. This will require efficient scaling of vector production, for example by developing vector production from stable cell lines [105,106] to reduce the cost and procedural burden of transient transfection that is the backbone of current viral vector approaches [107]. …”

Section: Expert Opinionmentioning

confidence: 99%

Lessons learned from lung and liver in-vivo gene therapy: implications for the future

Haasteren

Hyde

Gill

2018

Expert Opinion on Biological Therapy

View full text Add to dashboard Cite

Introduction: Ex-vivo gene therapy has had significant clinical impact over the last couple of years and in-vivo gene therapy products are being approved for clinical use. Gene therapy and gene editing approaches have huge potential to treat genetic disease and chronic illness. Areas covered: This article provides a review of in-vivo approaches for gene therapy in the lung and liver, exploiting non-viral and viral vectors with varying serotypes and pseudotypes to target-specific cells. Antibody responses inhibiting viral vectors continue to constrain effective repeat administration. Lessons learned from ex-vivo gene therapy and genome editing are also discussed. Expert opinion: The fields of lung and liver in-vivo gene therapy are thriving and a comparison highlights obstacles and opportunities for both. Overcoming immunological issues associated with repeated administration of viral vectors remains a key challenge. The addition of targeted small molecules in combination with viral vectors may offer one solution. A substantial bottleneck to the widespread adoption of in-vivo gene therapy is how to ensure sufficient capacity for clinical-grade vector production. In the future, the exploitation of gene editing approaches for in-vivo disease treatment may facilitate the resurgence of non-viral gene transfer approaches, which tend to be eclipsed by more efficient viral vectors.

show abstract

“…Compared with adenovirus and adeno-associated viral vectors, lentivirus possesses the ability to transport larger gene fragments thus ensuring earlier protein expression [31]. As a result, lentivirus is an attractive gene delivery system and is widely used in gene therapy [32]. The lentivirus expression vector, originated from the human immunodeficiency virus (HIV), is capable of infecting almost all mammalian cell types.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of c-Met in bone marrow mesenchymal stem cells improves their effectiveness in homing and repair of acute liver failure

Wang

Zhu

et al. 2017

Stem Cell Res Ther

View full text Add to dashboard Cite

BackgroundTransplantation of bone marrow-derived mesenchymal stem cells (BMSCs) has emerged as a novel therapy for acute liver failure (ALF). However, the homing efficiency of BMSCs to the injured liver sites appears to be poor. In this study, we aimed to determine if overexpression of c-Met in BMSCs could promote the homing ability of BMSCs to rat livers affected by ALF.MethodsOverexpression of c-Met in BMSCs (c-Met-BMSCs) was attained by transfection of naive BMSCs with the lenti-c-Met-GFP. The impact of transplanted c-Met-BMSCs on both homing and repair of ALF was evaluated and compared with lenti-GFP empty vector transfected BMSCs (control BMSCs).ResultsAfter cells were transfected with the lenti-c-Met-GFP vector, the BMSCs displayed very high expression of c-Met protein as demonstrated by Western blot. In addition, in vitro transwell migration assays showed that the migration ability of c-Met-BMSCs was significantly increased in comparison with that of control BMSCs (P < 0.05), and was dependent on hepatocyte growth factor (HGF). Furthermore, rats with ALF that received transplanted c-Met-BMSCs showed significantly improved homing ability to the injured liver; this was accompanied by elevated survival rates and liver function in the ALF rats. Parallel pathological examination further confirmed that transplantation of c-Met-BMSCs ameliorated liver injury with reduced hepatic activity index (HAI) scores, and that the effects of c-Met-BMSCs were more profound than those of control BMSCs.ConclusionsOverexpression of c-Met promotes the homing of BMSCs to injured hepatic sites in a rat model of ALF, thereby improving the efficacy of BMSC therapy for ALF repair.

show abstract

Challenges of up-scaling lentivirus production and processing

Cited by 88 publications

References 47 publications

Rational Design of Cancer Nanomedicine: Nanoproperty Integration and Synchronization

Rational Design of Cancer Nanomedicine: Nanoproperty Integration and Synchronization

Lessons learned from lung and liver in-vivo gene therapy: implications for the future

Overexpression of c-Met in bone marrow mesenchymal stem cells improves their effectiveness in homing and repair of acute liver failure

Contact Info

Product

Resources

About