Less phagocytosis of viral vectors by tethering with CD47 ectodomain

Alyami, Esmael M.; Tarar, Ammar; Peng, Ching‐An

doi:10.1039/d1tb01815a

Cited by 3 publications

(3 citation statements)

References 55 publications

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“…HEK293T cell culture supernatant containing lentiviral particles obtained on the third day was concentrated according to a previous report. 54 Briefly, 10 mL of virus-containing supernatant was mixed with 10 mL of Polybrene solution (320 μg/mL) and incubated at 37 °C for 30 min. Then, the mixture was centrifuged at 10 000 g for 10 min at 4 °C.…”

Section: Methodsmentioning

confidence: 99%

“…The collected supernatant that contains viruses were filtered through a 0.45 μm syringe filter. HEK293T cell culture supernatant containing lentiviral particles obtained on the third day was concentrated according to a previous report . Briefly, 10 mL of virus-containing supernatant was mixed with 10 mL of Polybrene solution (320 μg/mL) and incubated at 37 °C for 30 min.…”

Section: Methodsmentioning

confidence: 99%

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Inactivation of SARS-CoV-2 Spike Protein Pseudotyped Virus Infection Using ACE2-Tethered Gold Nanorods under Near-Infrared Laser Irradiation

Peng

Jokhio

Alkhaldi

et al. 2022

ACS Appl. Nano Mater.

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Since the angiotensin-converting enzyme 2 (ACE2) protein is abundant on the surface of respiratory cells in the lungs, it has been confirmed to be the entry-point receptor for the spike glycoprotein of SARS-CoV-2. As such, gold nanorods (AuNRs) functionalized with ACE2 ectodomain (ACE2ED) act not only as decoys for these viruses to keep them from binding with the ACE2-expressing cells but also as agents to ablate infectious virions through heat generated from AuNRs under near-infrared (NIR) laser irradiation. Using plasmid containing the SARS-CoV-2 spike protein gene (with a D614G mutation), spike protein pseudotyped viral particles with a lentiviral core and green fluorescent protein reporter were constructed and used for transfecting ACE2-expressing HEK293T cells. Since these viral particles behave like their coronavirus counterparts, they are the ideal surrogates of native virions for studying viral entry into host cells. Our results showed that, once the surrogate pseudoviruses with spike protein encounter ACE2ED-tethered AuNRs, these virions are entrapped, resulting in decreased viral infection to ACE2-expressing HEK293T cells. Moreover, the effect of photothermolysis created by ACE2ED-tagged AuNRs under 808-nm NIR laser irradiation for 5 min led to viral breakdown. In summary, ACE2ED-tethered AuNRs with dual functions (virus decoy and destruction) could have an intriguing advantage in the treatment of diseases involving rapidly mutating viral species such as SARS-CoV-2.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Inactivation of SARS-CoV-2 Spike Protein Pseudotyped Virus Infection Using ACE2-Tethered Gold Nanorods under Near-Infrared Laser Irradiation

Peng

Jokhio

Alkhaldi

et al. 2022

ACS Appl. Nano Mater.

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“…Furthermore, studies have demonstrated that LV vectors modified by the CD47ED fusion gene, incorporating extracellular domain-core of CD47 and streptavidin, can trigger phagocytosis of LV by antiphagocytic cells [ 147 ]. Notably, when BX795, an inhibitor of RIG-I, MDA5, and TBK1/IKKε complex downstream of TLR3, was employed to inhibit innate immune signals in cell lines, it resulted in significantly improved LV gene modification efficiency and enhanced LV transduction efficiency.…”

Section: Lentiviral Vector Therapymentioning

confidence: 99%

Innate Immune Response to Viral Vectors in Gene Therapy

Wang,

Shao

2023

Viruses

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Viral vectors play a pivotal role in the field of gene therapy, with several related drugs having already gained clinical approval from the EMA and FDA. However, numerous viral gene therapy vectors are currently undergoing pre-clinical research or participating in clinical trials. Despite advancements, the innate response remains a significant barrier impeding the clinical development of viral gene therapy. The innate immune response to viral gene therapy vectors and transgenes is still an important reason hindering its clinical development. Extensive studies have demonstrated that different DNA and RNA sensors can detect adenoviruses, adeno-associated viruses, and lentiviruses, thereby activating various innate immune pathways such as Toll-like receptor (TLR), cyclic GMP-AMP synthase–stimulator of interferon genes (cGAS-STING), and retinoic acid-inducible gene I–mitochondrial antiviral signaling protein (RLR-MAVS). This review focuses on elucidating the mechanisms underlying the innate immune response induced by three widely utilized viral vectors: adenovirus, adeno-associated virus, and lentivirus, as well as the strategies employed to circumvent innate immunity.

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Eradication of Cancer Cells Using Doxifluridine and Mesenchymal Stem Cells Expressing Thymidine Phosphorylase

Wang,

Peng,

Peng

2024

Bioengineering

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Gene-directed enzyme prodrug therapy (GDEPT) has been developed over several decades as a targeted cancer treatment aimed at minimizing toxicity to healthy cells. This approach involves three key components: a non-toxic prodrug, a gene encoding an enzyme that converts the prodrug into an active chemotherapy drug, and a gene carrier to target cancer cells. In this study, the prodrug doxifluridine was enzymatically converted into the chemotherapy drug 5-fluorouracil via thymidine phosphorylase, using human mesenchymal stem cells (hMSCs) as delivery vehicles. The hMSCs were first transduced with thymidine phosphorylase-encoded lentiviral vectors produced by HEK293T cells, then co-cultured with A549 adenocarcinoma cells in the presence of doxifluridine. The results showed that after 3 days of prodrug treatment, cell viability in both A549 cancer cells and hMSCs dropped by about 50%, and by day 5, viability had decreased to 10%. In summary, exogenous thymidine phosphorylase expressed in hMSCs successfully converted the non-toxic prodrug doxifluridine into the chemotherapy agent 5-fluorouracil, effectively eliminating both cancer cells and hMSCs within a short period.

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Less phagocytosis of viral vectors by tethering with CD47 ectodomain

Abstract: CD47 ectodomain tethered on the surface of lentiviral vectors endowing them with a phagocytosis-resistant feature.

Cited by 3 publications

References 55 publications

Inactivation of SARS-CoV-2 Spike Protein Pseudotyped Virus Infection Using ACE2-Tethered Gold Nanorods under Near-Infrared Laser Irradiation

Inactivation of SARS-CoV-2 Spike Protein Pseudotyped Virus Infection Using ACE2-Tethered Gold Nanorods under Near-Infrared Laser Irradiation

Innate Immune Response to Viral Vectors in Gene Therapy

Eradication of Cancer Cells Using Doxifluridine and Mesenchymal Stem Cells Expressing Thymidine Phosphorylase

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