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Human P53 adenoviral particles

Human P53 adenoviral particles

Cat.No. :  AD00268Z

Titer: ≥1x10^10 IFU/mL / ≥1x10^11 IFU/mL / ≥1x10^11 VP/mL / ≥1x10^12 VP/mL Size: 100 ul/500 ul/1 mL

Storage:  -80℃ Shipping:  Frozen on dry ice

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Adenovirus Particle Information

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Cat. No. AD00268Z
Target Gene TP53
Species Human
Product Type Adenoviral particle
Insert TP53
Titer Varies lot by lot, for example, ≥1x10^10 IFU/mL, ≥1x10^11 IFU/mL, ≥1x10^11 VP/mL etc.
Size Varies lot by lot, for example, 250 ul, 500 ul, 1 mL etc.
Storage Store at -80℃. Avoid multiple freeze/thaw cycles.
Shipping Frozen on dry ice
Creative Biogene ensures high-quality adenovirus particles by optimizing and standardizing production protocols and performing stringent quality control (QC). The specific QC experiments performed vary between adenovirus particle lots.
Endotoxin Endotoxins, primarily derived from Gram-negative bacteria, can trigger adverse immune responses. Endotoxin contamination is a significant concern in adenovirus production, especially for applications in animal studies and gene therapy. Creative Biogene utilizes rigorous endotoxin detection methods to monitor the endotoxin level in our produced adenovirus particles to ensure regulatory compliance.
Sterility Creative Biogene ensures that adenovirus products are free of any bacterial, fungal and other microbial contamination.
Ad5 E1 Detection All Creative Biogene adenoviruses are PCR tested to ensure that there are no detectable E1 sequences in the particles, which could be from revertants or external E1 contamination.
RCA Assays Adenovirus products originating at Creative Biogene are guaranteed to have undetectable replication-competent adenovirus (RCA). This quality control measure is important because there is always the possibility of wild-type contamination due to revertants or environmental sources.
PFU Titering All purified adenovirus preparations are tested for infectious titer. Creative Biogene's PFU test takes a few days longer but counts true plaques in HEK cells rather than estimating PFU titers via IHC staining or TCI50 of infected cells.
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The TP53 gene, commonly known as P53, is a key tumor suppressor gene that plays a critical role in maintaining genome stability and preventing cancer development. P53 is often referred to as the "guardian of the genome" and is able to regulate cell cycle arrest, DNA repair, apoptosis, and senescence in response to cellular stress (e.g., DNA damage or oncogenic activation). P53 gene mutations are present in more than 50% of human cancers, resulting in loss of its tumor suppressor function and uncontrolled cell proliferation. Restoring wild-type P53 activity in cancer cells has emerged as a promising therapeutic strategy, taking advantage of its ability to induce apoptosis or inhibit tumor growth. Human P53 adenoviral particles are genetically engineered recombinant adenoviral vectors designed to deliver the wild-type TP53 gene to target cells. These particles leverage the natural infectivity of adenoviruses and are able to efficiently transduce a variety of cell types, including cancer cells. The adenoviral backbone has been modified to ensure safety by removing viral replication genes (E1/E3 deletion) to make it replication-defective while retaining high transduction efficiency. After infection, the delivered P53 gene is expressed, restoring normal P53 function in tumor cells and eliciting anti-cancer effects. These vectors are widely used in gene therapy research, especially in preclinical and clinical studies of P53-deficient cancers. Advantages include high delivery efficiency, scalability, and the ability to induce stable transgene expression.

Diffuse-type gastric cancer (GC) frequently exhibits peritoneal metastasis, leading to a poor prognosis. As diffuse-type GC cells often carry genetic alterations in the tumor suppressor gene p53, p53 restoration may be an effective strategy to prevent peritoneal metastasis of GC. Here, researchers investigated the therapeutic potential of adenoviral vectors expressing p53 against peritoneal metastasis of diffuse GC cells. Three diffuse human GC cell types with different p53 status (p53–wild type NUGC-4, p53–mutant type GCIY, and p53–null type KATOIII) were used to evaluate the therapeutic potential of p53 activation induced by a replication-defective adenovirus expressing p53, Ad-p53, and an oncolytic adenovirus, OBP-702. OBP-702 induced significantly stronger antitumor effects than Ad-p53 in GC cells under both normal and sphere-forming culture conditions, through robust induction of p53-mediated apoptosis and autophagy, as well as receptor tyrosine kinase inhibition. In vivo experiments showed that intraperitoneal injection of OBP-702 significantly inhibited the peritoneal metastasis of NUGC-4 and GCIY cells compared with Ad-p53, thereby prolonging the survival of mice.

A xenograft peritoneal metastasis model involving p53-intact NUGC-4 cells was used to investigate the therapeutic potential of Ad-p53 and OBP-702 against peritoneal metastasis of diffuse-type GC cells. NUGC-4-RFP cells expressing RFP were inoculated into mice peritoneally, and 14 days later, the mice were injected intraperitoneally with Ad-p53 or OBP-702 every other day for a total of three injections (Figure 1A). Intraperitoneal injection of OBP-702, but not Ad-p53, significantly suppressed the intensity of RFP in peritoneal metastasis of NUGC-4 cells (Figure 1B and C). Administration of OBP-702 reduced the incidence of hemorrhagic ascites, but administration of Ad-p53 did not (Figure 1D). These results suggest that intraperitoneal administration of OBP-702 has the therapeutic potential to inhibit peritoneal metastasis of p53-intact diffuse-type GC cells.

Figure 1. Antitumor effect of Ad-p53 and OBP-702 against peritoneal metastasis of p53-intact NUGC-4 cells.Figure 1. Antitumor effect of Ad-p53 and OBP-702 against peritoneal metastasis of p53-intact NUGC-4 cells. (Hori N, et al. 2023)

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Customer Reviews
Smooth Experimental Workflow

Incorporating Creative Biogene’s Human P53 adenoviral particles into my experimental workflow was seamless. The straightforward protocol and particle performance minimized optimization time.

Canada

11/03/2024

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