Disease relevance of DC-Chol

• The objectives of this study were to examine the toxicities of employing the human HLA-A2, HLA-B13 and the murine H-2K genes to generate tumor regression in patients with different cancer types via DC-Chol/DOPE cationic liposomes [1].
• When virus complexed with DC-Chol/DOPE was used to transduce human mesothelioma xenografts, transduction was enhanced four- to fivefold compared to that for virus alone [2].
• Further studies to investigate the use of HLA-A2 DC-Chol/DOPE cationic liposomes for immunotherapy of cervical and ovarian cancers are warranted [1].
• Cationic lipid DC-Chol induces an improved and balanced immunity able to overcome the unresponsiveness to the hepatitis B vaccine [3].
• The ability to induce a protective response against Helicobacter pylori infection has been investigated by systemic immunization of mice with urease formulated with the cationic lipid DC Chol [4].

High impact information on DC-Chol

• Formulation of the AdV vector with DS/DOPE and DC-Chol/DOPE resulted in transgene expression targeted only to the airway epithelial cells with minimal expression in alveolar cells, while AdV alone caused high alveolar transduction [5].
• IFN-gamma was significantly elevated at day 7 in mice receiving only the AdV vector compared to the AdV vector formulated with DS/DOPE, DC-Chol/DOPE, or dexamethasone [5].
• The Sit-G-liposome/DNA complex was composed of Tfx-20 reagent (Tfx), ie synthetic cationic lipid [N,N,N',N'-tetramethyl-N,N'-bis(2-hydroxyethyl)-2,3-di(oleoyloxy)-1,4-butanediammonium iodide] with L-dioleoylphosphatidylethanolamine (DOPE), 3 beta[N-(N',N'-dimethylaminoethane)-carbamoyl]cholesterol (DC-Chol) and Sit-G with plasmid DNA [6].
• Building upon our earlier use of cationic liposomes formulated from 3beta-[N-(N',N'-dimethylaminoethane)carbamoyl] cholesterol (DC-Chol) and dioleoyl-L-alpha-phosphatidyl-ethanolamine (DOPE), we describe studies using two cationic viral peptides, mu (mu) and Vp1, as potential enhancers for cationic liposome-mediated transfection [7].
• Ten subjects received plasmid DNA expressing the CFTR cDNA complexed with DC-Chol/DOPE cationic liposomes, whilst two subjects received placebo [8].

Chemical compound and disease context of DC-Chol

• We compared the transfection activity and toxicity of CHDTAEA with its nondisulfide analogue and cholesteryl N-(dimethylaminoethyl) carbamate (DC-Chol) [9].
• One of the liposome formulations, DC-Chol liposomes, is used in a gene therapy clinical trial for melanoma [10].

Biological context of DC-Chol

• The presence of 20 mM mannose significantly inhibited the transfection efficiency of pCMV-Luc complexed with Man-C4-Chol/DC- Chol/DOPE(3:3:4) and Man-C4-Chol/DOPE(6:4) liposomes [11].
• We demonstrate high rates of transfection with the reporter gene pSV40 beta gal using DC-Chol/DOPE cationic liposomes and lower rates with the novel polyamine cationic liposomes ACHx/DC-Chol/DOPE and ACO/DC-Chol/DOPE [12].
• High gene expression of pCMV-Luc was observed in the liver after intravenously injecting mice with Man-C4-Chol/DOPE(6:4) liposomes, whereas DC-Chol/DOPE(6:4) liposomes only showed marked expression in the lung [11].
• Induction of apoptosis was much greater than that by commercially available DC-Chol liposomes [13].
• The use of DC-Chol increased antibody responses in responding BALB/c mice, induced more consistent IgG1 and IgG2a antibody responses in OF1 mice and overcame the nonresponse to HBsAg in B10.M mice [3].

Anatomical context of DC-Chol

• Our previous work has shown that cationic liposomes formulated from 3 beta-[N-(N',N'-dimethylaminoethane)carbamoyl] cholesterol (DC-Chol) and dioleoyl-L-alpha-phosphatidylethanolamine (DOPE) could achieve high transfection levels in a neuronal cell line (McQuillin et al. Neuroreport 1997; 8: 1481-1484) [14].
• Endothelial cells transfected with HSV-thymidine kinase using DC-Chol/DOPE demonstrated 3 log10 increased cytotoxicity compared with controls when exposed to the prodrug ganciclovir, thereby demonstrating significant biological effect [12].
• The liposomes of CHDTAEA had more than 2 orders of magnitude greater transfection activity than DC-Chol in CHO cells and 7 times greater transfection activity in SKnSH cells [9].
• Reporter gene (beta-gal) or brain-derived neurotrophic factor (BDNF) cDNA containing a pCMV promoter complexed with DC-Chol liposomes was injected into the intact rat spinal cord gray matter [15].
• A cell line derived from sensory neurons was transfected with high efficiency using cationic liposomes, formulated from 3 beta [N-(N',N'-dimethylaminoethane)carbamoyl]-cholesterol (DC-Chol) and dioleoyl L-alpha-phosphatidylethanolamine (DOPE) [16].

Associations of DC-Chol with other chemical compounds

• Cationic emulsion was prepared with varying compositions of 3 beta [N-(N',N'-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol), dioleoylphosphatidyl ethanolamine (DOPE), caster oil and Tween 80 [17].
• Gal-C4-Chol/DC-Chol/DOPE(3:3:4) liposomes, consisting of 3:3:4 mixtures of Gal-C4-Chol, 3beta[N',N', N'-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol), and dioleoylphosphatidylethanolamine (DOPE), showed higher transfection activity and [32P]DNA uptake than DC-Chol/DOPE(6:4) liposomes [18].
• PURPOSE: The purpose of this study was to evaluate protamine-mediated gene transfection by liposomes with a novel cationic cholesterol derivative (I) compared to those with DC-Chol or DOTMA (Lipofectin) [19].
• In addition to DOTMA liposomes, liposomes composed of 1,2-dioleoyl-3-trimethylammonium propane chloride (DOTAP) and 3beta[N-(N', N'-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol) also enhance the level of gene expression in animals transfected by DNA/DOTMA complexes [20].

Gene context of DC-Chol

• The DC-Chol induced a balanced Th1/Th2 response, which enabled mice to overcome the inherited unresponsiveness to HBsAg encountered with aluminum-adjuvanted vaccine [3].
• Thus, the DC-Chol provides a signal to switch on both Th1 and Th2 responses, which may have important implications for vaccination against hepatitis B virus, as well as for enhancing weak immunogenicity of other recombinant purified antigens in a nonresponder population [3].
• We demonstrated that DC-Chol and Zymosan are the most efficient mucosal candidate immunoadjuvants that generate a strong increase of CCL20 secretion by the two epithelial cell lines and the maturation of dendritic and Langerhans cells, respectively [21].
• The results of these preclinical studies clearly indicated that transcriptional repressors, which downregulate HER2/neu overexpression, can be an effective regimen for cancer treatment in a gene therapy format combined with an appropriate gene delivery system such as the cationic liposome DC-Chol or replication-deficient adenovirus vector [22].
• Thermodynamic aspects and biological profile of CDAN/DOPE and DC-Chol/DOPE lipoplexes [23].

Analytical, diagnostic and therapeutic context of DC-Chol

• Colonies from cells infected using centrifugation were positive 27% of the time, while the combined approach had positive colonies 31 and 50% of the time for DC-Chol and Lipofectamine, respectively [24].
• DC-Chol/DOPE-mediated transfection was confirmed using a RT-PCR protocol capable of differentiating between untranscribed plasmid DNA and RNA generated from the transfected vector [14].
• No such biphasic effects are seen with respect to the binding between DC-Chol/DOPE and pDNA that appears to be otherwise instantaneous with no rehydration effects [23].
• The DNA complexation and condensation properties of two established cationic liposome formulations, CDAN/DOPE (50:50, m/m; Trojene) and DC-Chol/DOPE (60:40, m/m), were investigated by using a combination of isothermal titration calorimetry (ITC), circular dichroism (CD), photon correlation spectroscopy (PCS), and turbidity assays [23].
• DOTAP/DOPE and DC-Chol/DOPE lipoplexes for gene delivery studied by circular dichroism and other biophysical techniques [25].

References