Random Integration Analysis of Recombinant Adeno-Associated Virus 6 Packaged in Sf9 Insect Cells

Zhang, M. H.; Liu, X. M.; Zhang, Cheng

doi:10.1134/s0026893323040209

Cited by 2 publications

(3 citation statements)

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“…AAV has genotoxicity, and can be randomly integrated into the host gene locus. The exact mechanism of the random integration of AAV into the host genome is still unknown, but random integration is known to be dose-dependent [ 31 , 32 ]. Therefore, it is important to ascertain the lowest dose of AAV to ensure sufficient efficacy with safety.…”

Section: Adeno-associated Virus Gene Therapy For the Treatment Of Hem...mentioning

confidence: 99%

“…Therefore, larger amounts of AAV may be injected for KI efficiency when using more than one type of AAV than when using a single AAV. Administration of high-dose AAV increases the risk of immune reactions and random integration [ 31 , 96 ]. In addition, long-term expression of AAV allows the CRISPR system to function continuously in the body.…”

Section: In Vivo Gene Knock-in Strategies For the Treatment Of Hemoph...mentioning

confidence: 99%

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In vivo LNP-CRISPR Approaches for the Treatment of Hemophilia

Lee,

Han

2024

Mol Diagn Ther

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Hemophilia is a genetic disorder that is caused by mutations in coagulation factor VIII (hemophilia A) or IX (hemophilia B) genes resulting in blood clotting disorders. Despite advances in therapies, such as recombinant proteins and products with extended half-lives, the treatment of hemophilia still faces two major limitations: the short duration of therapeutic effect and production of neutralizing antibodies against clotting factors (inhibitor). To overcome these limitations, new hemophilia treatment strategies have been established such as gene therapy, bispecific antibody, and rebalancing therapy. Although these strategies have shown promising results, it is difficult to achieve a permanent therapeutic effect. Advances in the clustered regularly interspaced short palindromic repeat (CRISPR) technology have allowed sustainable treatment by correcting mutated genes. Since genome editing generates irreversible changes in host genome, safety must be ensured by delivering target organs. Therefore, the delivery tool of the CRISPR system is crucial for safe, accurate, and efficient genome editing. Recently, non-viral vector lipid nanoparticles (LNPs) have emerged as safer tools for delivering CRISPR systems than other viral vectors. Several previous hemophilia pre-clinical studies using LNP-CRISPR showed that sufficient and sustainable therapeutic effects, which means that LNP-CRISPR-mediated genome-editing therapy can be a valid option for the treatment of hemophilia. In this paper, we summarize the latest advancements in the successful treatment of hemophilia and the potential of CRISPR-mediated genome-editing therapy using LNPs.

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Section: Adeno-associated Virus Gene Therapy For the Treatment Of Hem...mentioning

confidence: 99%

Section: In Vivo Gene Knock-in Strategies For the Treatment Of Hemoph...mentioning

confidence: 99%

In vivo LNP-CRISPR Approaches for the Treatment of Hemophilia

Lee,

Han

2024

Mol Diagn Ther

View full text Add to dashboard Cite

show abstract

“…Alternatively, its main drawbacks are include the need for a large amount of organic solvent, which is difficult to remove, lower EE for water-soluble drugs, small-scale production, production of poly-disperse MLVs, no particle size control, time-consuming procedure, and need for sterilization. 43,44 Solvent injection (SJ) involves dissolving lipids and lipophilic drugs in an organic solvent (ethanol and ether) to obtain a lipid-phase stage. The lipid-phase stage has been employed in numerous aqueous phases for the preparation of liposomal nanoformulations.…”

Section: Techniques For the Preparation Of Liposomesmentioning

confidence: 99%