Non-Integrating Lentiviral Vectors in Clinical Applications: A Glance Through

Gurumoorthy, Narmatha; Nordin, Fazlina; Tye, Gee Jun; Zaman, Wan Safwani Wan Kamarul; Ng, Min Hwei

doi:10.3390/biomedicines10010107

Cited by 31 publications

(18 citation statements)

References 142 publications

(111 reference statements)

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“…Non-integrating LV systems have been proposed as a transient delivery method. Non-integrating LVs for the transient delivery of CRISPR components were designed via the mutation of the viral integrase gene or the long terminal repeats (LTRs) that carry important integration signals [ 132 , 133 ]. Alternatively, one could use non-viral delivery methods such as lipid-based ribonucleoproteins (RNPs) [ 134 , 135 ], polymer-based RNPs [ 136 ], or inorganic materials for CRISPR-Cas delivery [ 137 ].…”

Section: Challenges and Potential Solutions In Designing A Crispr-cas...mentioning

confidence: 99%

A CRISPR-Cas Cure for HIV/AIDS

Hussein

Molina

Berkhout

et al. 2023

IJMS

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Human immunodeficiency virus (HIV) infections and HIV-induced acquired immunodeficiency syndrome (AIDS) continue to represent a global health burden. There is currently no effective vaccine, nor any cure, for HIV infections; existing antiretroviral therapy can suppress viral replication, but only as long as antiviral drugs are taken. HIV infects cells of the host immune system, and it can establish a long-lived viral reservoir, which can be targeted and edited through gene therapy. Gene editing platforms based on the clustered regularly interspaced palindromic repeat-Cas system (CRISPR-Cas) have been recognized as promising tools in the development of gene therapies for HIV infections. In this review, we evaluate the current landscape of CRISPR-Cas-based therapies against HIV, with an emphasis on the infection biology of the virus as well as the activity of host restriction factors. We discuss the potential of a combined CRISPR-Cas approach that targets host and viral genes to activate antiviral host factors and inhibit viral replication simultaneously. Lastly, we focus on the challenges and potential solutions of CRISPR-Cas gene editing approaches in achieving an HIV cure.

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Section: Challenges and Potential Solutions In Designing A Crispr-cas...mentioning

confidence: 99%

A CRISPR-Cas Cure for HIV/AIDS

Hussein

Molina

Berkhout

et al. 2023

IJMS

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“…Transcription factor delivery is currently achieved via viral infection, in which viral vectors integrate into the host cell genome ( Vignoles et al, 2019 ). Despite the efficacy of viral vectors, this approach is associated with risks, including insertional mutagenesis, transgene integration, cellular senescence, strong immunogenicity, and viral infection ( Gurumoorthy et al, 2022 ). Third, in the small molecule-mediated conversion approach in vivo , cell type specificity is difficult to achieve, and toxicity is a challenge ( Hu et al, 2018 ).…”

Section: Challenges and Controversiesmentioning

confidence: 99%

Application and prospects of somatic cell reprogramming technology for spinal cord injury treatment

Yang

Pan

Wang

et al. 2022

Front. Cell. Neurosci.

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Spinal cord injury (SCI) is a serious neurological trauma that is challenging to treat. After SCI, many neurons in the injured area die due to necrosis or apoptosis, and astrocytes, oligodendrocytes, microglia and other non-neuronal cells become dysfunctional, hindering the repair of the injured spinal cord. Corrective surgery and biological, physical and pharmacological therapies are commonly used treatment modalities for SCI; however, no current therapeutic strategies can achieve complete recovery. Somatic cell reprogramming is a promising technology that has gradually become a feasible therapeutic approach for repairing the injured spinal cord. This revolutionary technology can reprogram fibroblasts, astrocytes, NG2 cells and neural progenitor cells into neurons or oligodendrocytes for spinal cord repair. In this review, we provide an overview of the transcription factors, genes, microRNAs (miRNAs), small molecules and combinations of these factors that can mediate somatic cell reprogramming to repair the injured spinal cord. Although many challenges and questions related to this technique remain, we believe that the beneficial effect of somatic cell reprogramming provides new ideas for achieving functional recovery after SCI and a direction for the development of treatments for SCI.

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“…New potential applications for LVs have emerged. Recently, the use of LVs gained importance as a possible vaccination platform that uses integrating as well as non-integrating LVs to target infectious diseases [ 6 , 7 ]. The broad range of diseases that can be treated with LVs and emerging applications will lead to an increased need for efficient LV bioprocessing [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Scaling Up of Steric Exclusion Membrane Chromatography for Lentiviral Vector Purification

et al. 2023

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Lentiviral vectors (LVs) are widely used in clinical trials of gene and cell therapy. Low LV stability incentivizes constant development and the improvement of gentle process steps. Steric exclusion chromatography (SXC) has gained interest in the field of virus purification but scaling up has not yet been addressed. In this study, the scaling up of lentiviral vector purification by SXC with membrane modules was approached. Visualization of the LVs captured on the membrane during SXC showed predominant usage of the upper membrane layer. Furthermore, testing of different housing geometries showed a strong influence on the uniform usage of the membrane. The main use of the first membrane layer places a completely new requirement on the scaling of the process and the membrane modules. When transferring the SXC process to smaller or larger membrane modules, it became apparent that scaling of the flow rate is a critical factor that must be related to the membrane area of the first layer. Performing SXC at different scales demonstrated that a certain critical minimum surface area-dependent flow rate is necessary to achieve reproducible LV recoveries. With the presented scaling approach, we were able to purify 980 mL LVs with a recovery of 68%.

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Non-Integrating Lentiviral Vectors in Clinical Applications: A Glance Through

Cited by 31 publications

References 142 publications

A CRISPR-Cas Cure for HIV/AIDS

A CRISPR-Cas Cure for HIV/AIDS

Application and prospects of somatic cell reprogramming technology for spinal cord injury treatment

Scaling Up of Steric Exclusion Membrane Chromatography for Lentiviral Vector Purification

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