Hydrodynamic Delivery

Suda, Takafumi; Liu, Dexi

doi:10.1016/bs.adgen.2014.10.002

Cited by 20 publications

(17 citation statements)

References 131 publications

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“…As a negative control for many of the experiments, we used the original adenovirus vector Ad-Fc-CTP-Flag. Since liver shows the highest level of transgene expression following infection with adenovirus [12], we first confirmed TFF2 mRNA expression in the liver of Tff2-null mice after a single dose (5 × 10 8 pfu per mouse) of Ad-Tff2-CTP-Flag versus Ad-Tff2. In both cohorts of mice, similar kinetic profiles of TFF2 mRNA transcripts were observed in the liver, with maximum abundance at day 4 and a decline to basal levels by the end of third week (Fig.…”

Section: Adenovirus-mediated Delivery Of Fusion Tff2-ctpflagmentioning

confidence: 74%

Therapeutic potential of adenovirus-mediated TFF2-CTP-Flag peptide for treatment of colorectal cancer

et al. 2018

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TFF2 is a small, secreted protein with anti-inflammatory properties. We previously have shown that TFF2 gene delivery via adenovirus (Ad-Tff2) suppresses colon tumor growth in colitis associated cancer. Therefore, systemic administration of TFF2 peptide could potentially provide a similar benefit. Because TFF2 shows a poor pharmacokinetic, we sought to modify the TFF2 peptide in a manner that would lower its clearance rate but retain bioactivity. Given the absence of a sequencebased prediction of TFF2 functionality, we chose to genetically fuse the C-terminus of TFF2 with the carboxyl-terminal peptide of human chorionic gonadotropin β subunit, and inserted into adenoviral vector that expresses Flag. The resulting Ad-Tff2-CTP-Flag construct translates into a TFF2 fused with two CTP and three Flag motifs. Administered Ad-Tff2-CTPFlag decreased tumorigenesis and suppressed the expansion of myeloid cells in vivo. The fusion peptide TFF2-CTP-Flag delivered by adenovirus Ad-Tff2-CTP-Flag as well purified recombinant fusion TFF2-CTP-Flag was retained in the blood longer compared with wild-type TFF2 delivered by Ad-Tff2 or recombinant TFF2. Consistently, purified recombinant fusion TFF2-CTP-Flag suppressed expansion of myeloid cells by down-regulating cyclin D1 mRNA in vitro. Here, we demonstrate for the very first time the retained bioactivity and possible pharmacokinetic advantages of TFF2 with a modified C-terminus.

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Section: Adenovirus-mediated Delivery Of Fusion Tff2-ctpflagmentioning

confidence: 74%

Therapeutic potential of adenovirus-mediated TFF2-CTP-Flag peptide for treatment of colorectal cancer

et al. 2018

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“…However, hepatic delivery remains the Achilles heel in non-viral gene therapy studies aiming at clinical trials. [42][43][44] It remains to be seen whether the SB transposons can be used in the in vivo approach as successfully as they are being used to treat blood cancers in human patients. 71 …”

Section: Discussionmentioning

confidence: 99%

“…The injection route, properties of the vasculature and of the target organ (the liver), as well as the direction of flow after hydrodynamics-based injection are important parameters that differ substantially between mice and large animals. 4,41,42 Until recently, the efficacy of non-viral DNA delivery to treat large animals has been discouraging. 4,[42][43][44] The authors developed and examined the potential of catheter-mediated infusion via the hepatic veins wherein targeted liver tissues are isolated from the blood flow by balloon occlusion of blood vessels.…”

Section: Introductionmentioning

confidence: 99%

“…4,41,42 Until recently, the efficacy of non-viral DNA delivery to treat large animals has been discouraging. 4,[42][43][44] The authors developed and examined the potential of catheter-mediated infusion via the hepatic veins wherein targeted liver tissues are isolated from the blood flow by balloon occlusion of blood vessels. In dogs aged ‡3 months, 41 detectable expression of the reporter enzyme canine serum alkaline phosphatase (cSEAP) was achieved for up to 6 weeks, a duration that is too short for clinical application, which requires extended gene expression.…”

Section: Introductionmentioning

confidence: 99%

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Prolonged Expression of Secreted Enzymes in Dogs After Liver-Directed Delivery ofSleeping BeautyTransposons: Implications for Non-Viral Gene Therapy of Systemic Disease

et al. 2017

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The non-viral, integrating Sleeping Beauty (SB) transposon system is efficient in treating systemic monogenic disease in mice, including hemophilia A and B caused by deficiency of blood clotting factors and mucopolysaccharidosis types I and VII caused by a-L-iduronidase (IDUA) and b-glucuronidase (GUSB) deficiency, respectively. Modified approaches of the hydrodynamics-based procedure to deliver transposons to the liver in dogs were recently reported. Using the transgenic canine reporter secreted alkaline phosphatase (cSEAP), transgenic protein in the plasma was demonstrated for up to 6 weeks post infusion. This study reports that immunosuppression of dogs with gadolinium chloride (GdCl 3 ) prolonged the presence of cSEAP in the circulation up to 5.5 months after a single vector infusion. Transgene expression declined gradually but appeared to stabilize after about 2 months at approximately fourfold baseline level. Durability of transgenic protein expression in the plasma was inversely associated with transient increase of liver enzymes alanine transaminase and aspartate transaminase in response to the plasmid delivery procedure, which suggests a deleterious effect of hepatocellular toxicity on transgene expression. GdCl 3 treatment was ineffective for repeat vector infusions. In parallel studies, dogs were infused with potentially therapeutic transposons. Activities of transgenic IDUA and GUSB in plasma peaked at 50-350% of wildtype, but in the absence of immunosuppression lasted only a few days. Transposition was detectable by excision assay only when the most efficient transposase, SB100X, was used. Dogs infused with transposons encoding canine clotting factor IX (cFIX) were treated with GdCl 3 and showed expression profiles similar to those in cSEAP-infused dogs, with expression peaking at 40% wt (2 lg/mL). It is concluded that GdCl 3 can support extended transgene expression after hydrodynamic introduction of SB transposons in dogs, but that alternative regimens will be required to achieve therapeutic levels of transgene products.

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“…Since its discovery, it has become the simplest and most efficient method to deliver nucleic acids to the liver 67 . Hydrodynamic pressure is produced by rapidly administration of a large volume of a nucleic acid solution to induce the formation of temporary pores on the cell membrane of endothelial cells and facilitate the nucleic acid to enter cells 68,69 . Hydrodynamic injection has been widely utilized in a variety of applications for the delivery of proteins, small interfering RNA (siRNA), DN A, and even cancer cells.…”

Section: Physical and Non-viral Delivery Of Crispr-cas9mentioning

confidence: 99%

Delivery strategies of the CRISPR-Cas9 gene-editing system for therapeutic applications

Liu

zhang

Líu

et al. 2017

Journal of Controlled Release

433

399

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The CRISPR-Cas9 genome-editing system is a part of the adaptive immune system in archaea and bacteria to defend against invasive nucleic acids from phages and plasmids. The single guide RNA (sgRNA) of the system recognizes its target sequence in the genome, and the Cas9 nuclease of the system acts as a pair of scissors to cleave the double strands of DNA. Since its discovery, CRISPR-Cas9 has become the most robust platform for genome engineering in eukaryotic cells. Recently, the CRISPR-Cas9 system has triggered enormous interest in therapeutic applications. CRISPR-Cas9 can be applied to correct disease-causing gene mutations or engineer T cells for cancer immunotherapy. The first clinical trial using the CRISPR-Cas9 technology was conducted in 2016. Despite the great promise of the CRISPR-Cas9 technology, several challenges remain to be tackled before its successful applications for human patients. The greatest challenge is the safe and efficient delivery of the CRISPR-Cas9 genome-editing system to target cells in human body. In this review, we will introduce the molecular mechanism and different strategies to edit genes using the CRISPR-Cas9 system. We will then highlight the current systems that have been developed to deliver CRISPR-Cas9 in vitro and in vivo for various therapeutic purposes.

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Hydrodynamic Delivery

Cited by 20 publications

References 131 publications

Therapeutic potential of adenovirus-mediated TFF2-CTP-Flag peptide for treatment of colorectal cancer

Therapeutic potential of adenovirus-mediated TFF2-CTP-Flag peptide for treatment of colorectal cancer

Prolonged Expression of Secreted Enzymes in Dogs After Liver-Directed Delivery ofSleeping BeautyTransposons: Implications for Non-Viral Gene Therapy of Systemic Disease

Delivery strategies of the CRISPR-Cas9 gene-editing system for therapeutic applications

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