1.
A review on cationic lipids with different linkers for gene delivery.
Zhi, D, Bai, Y, Yang, J, Cui, S, Zhao, Y, Chen, H, Zhang, S
Advances in colloid and interface science. 2018;:117-140
Abstract
Cationic lipids have become known as one of the most versatile tools for the delivery of DNA, RNA and many other therapeutic molecules, and are especially attractive because they can be easily designed, synthesized and characterized. Most of cationic lipids share the common structure of cationic head groups and hydrophobic portions with linker bonds between both domains. The linker bond is an important determinant of the chemical stability and biodegradability of cationic lipid, and further governs its transfection efficiency and cytotoxicity. Based on the structures of linker bonds, they can be grouped into many types, such as ether, ester, amide, carbamate, disulfide, urea, acylhydrazone, phosphate, and other unusual types (carnitine, vinyl ether, ketal, glutamic acid, aspartic acid, malonic acid diamide and dihydroxybenzene). This review summarizes some research results concerning the nature (such as the structure and orientation of linker groups) and density (such as the spacing and the number of linker groups) of linker bond for improving the chemical stability, biodegradability, transfection efficiency and cytotoxicity of cationic lipid to overcome the critical barriers of in vitro and in vivo transfection.
2.
Multiple associated variants increase the heritability explained for plasma lipids and coronary artery disease.
Tada, H, Won, HH, Melander, O, Yang, J, Peloso, GM, Kathiresan, S
Circulation. Cardiovascular genetics. 2014;(5):583-7
-
-
Free full text
-
Abstract
BACKGROUND Plasma lipid levels as well as coronary artery disease (CAD) have been shown to be highly heritable with estimates ranging from 40% to 60%. However, top variants detected by large-scale genome-wide association studies explain only a fraction of the total variance in plasma lipid phenotypes and CAD. METHODS AND RESULTS We performed a conditional and joint association analysis using summary-level statistics from 2 large genome-wide association meta-analyses: the Global Lipids Genetics Consortium (GLGC) study, and the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) study. There were 100 184 individuals from 46 GLGC studies for plasma lipids, and 22 233 cases and 64 762 controls from 14 studies for CAD. We detected several loci where multiple independent single-nucleotide polymorphisms were associated with lipid traits within a locus (12 out of 33 loci for high-density lipoprotein cholesterol, 10 of 35 loci for low-density lipoprotein cholesterol, 13 of 44 loci for total cholesterol, and 8 of 28 loci for triglycerides), reaching genome-wide significance (P<5×10(-8)), nearly doubling the heritability explained by genome-wide association studies (from 3.6 to 7.6% for high-density lipoprotein cholesterol, from 5.0 to 8.8% for low-density lipoprotein cholesterol, from 5.5 to 8.8% for total cholesterol, and from 5.7 to 8.5% for triglycerides). Multiple single-nucleotide polymorphisms were also associated with CAD (3 of 15 loci; an increase from 9.6% to 11.4% of heritability explained). CONCLUSIONS These results demonstrate that a portion of the missing heritability for lipid traits and CAD can be explained by multiple variants at each locus.
3.
Solid-state nuclear magnetic resonance measurements of HIV fusion peptide to lipid distances reveal the intimate contact of beta strand peptide with membranes and the proximity of the Ala-14-Gly-16 region with lipid headgroups.
Qiang, W, Yang, J, Weliky, DP
Biochemistry. 2007;(17):4997-5008
-
-
Free full text
-
Abstract
Human immunodeficiency virus (HIV) infection begins with fusion between viral and host cell membranes and is catalyzed by the HIV gp41 fusion protein. The approximately 20 N-terminal apolar residues of gp41 are called the HIV fusion peptide (HFP), interact with the host cell membrane, and play a key role in fusion. In this study, the membrane location of peptides which contained the HFP sequence (AVGIGALFLGFLGAAGSTMGARS) was probed in samples containing either only phospholipids or phospholipids and cholesterol. Four HFPs were examined which each contained 13CO labeling at three sequential residues between G5 and G16. The 13CO chemical shifts indicated that HFP had predominant beta strand conformation over the labeled residues in the samples. The internuclear distances between the HFP 13CO groups and the lipid 31P atoms were measured using solid-state nuclear magnetic resonance rotational-echo double-resonance experiments. The shortest 13CO-31P distances of 5-6 A were observed for HFP labeled between A14 and G16 and correlated with intimate association of beta strand HFP and membranes. These results were confirmed with measurements using HFPs singly labeled with 13CO at A6 or A14. To our knowledge, these data are the first measurements of distances between HIV fusion peptide nuclei and lipid P, and qualitative models of the membrane location of oligomeric beta strand HFP which are consistent with the experimental data are presented. Observation of intimate contact between beta strand HFP and membranes provides a rationale for further investigation of the relationship between structure and fusion activity for this conformation.