How plasma protein binding can influence biodistribution and activity of antisense oligonucleotides and plasmid DNA?
Plasma proteins binding can significantly affect the distribution and clearance of drugs, applicable even to antisense oligonucleotides and plasmid (recombinant) DNA used in treatment of various diseases.
Antisense oligonuclueotides bind to plasma proteins, which slow their metabolism or clearance from the kidneys. As it is seen that most of the oligonucleotides that fall in the size range of 3 to 6 nm or less are easily cleared through renal (kidney) route. Decreased renal clearance increases the half life of the antisense oligonucleotides (about 1 to 3 days, as reported in a study for liver disease).
Secondly, plasma protein binding can serve as a depot (reserviour) for free (unbound) oligonucleotides which can be relased slowly slowly by various elimination processes of the body. This prolongs duration of action of antisense oligonucleotides.
In case of plasmid DNA, plasma protein binding protects the DNA complex from degradation. This increased plasmid (recombinant) DNA uptake by cells / tissues, enhancing therapy efficiency.
How plasma protein binding can influence biodistribution and activity of antisense oligonucleotides and plasmid DNA?
1 Which of the following represents one of the mechanisms by which antisense agents exert their effect? a. A short DNA sequence binds to specific regions of complementary mRNA, inducing a nuclease that promotes translation to the corresponding protein b. Antisense oligonucleotides prevent the natural silencing of targeted mRNA sequences C. A short DNA sequence binds to specific regions of complementary mRNA, inducing a nuclease that cleaves the mRNA d. Antisense oligonucleotides inhibit all types of gene splicing 2 The...
1. How can antisense RNA inhibit translation? a.An antisense RNA makes a protein that inhibits translation. b.An antisense RNA binds to a transcript and inhibits translation. c.An antisense RNA forms a single stranded structure that inhibits translation. d.An antisense RNA binds to a translation inhibitor protein and prevents translation. 2. which of the following is true with regards to enhancer sequences? a.represor proteins bind to them b. they may be located eiter upstream or downstream of the promoter c.they are...
The activity of would be quickly undone in the absence of single-stranded binding protein. O DNA polymerase | O DNA polymerase III O DNA ligase O DNA helicase O primase
With regards to Spinal Muscular Atrophy and the Antisense. 1. The role of the protein targeted by the antisense [3pts] 2. The specific sequence of the mRNA targeted [3pts] 3. The specific sequence of your antisense molecule [3pts] 4. The specific amino acid sequence affected by binding of the antisense molecule [3pts] 5.Why you targeted that specific sequence [3pts] 6. Modifications made to the antisense molecule to enhance its resistance to RNAse H; if no modifications were done for your...
How does ribosome binding affect the final level of protein produced from a DNA sequence? Only one question at a time; only one chance to answer. Question 1 0.5 pts How does ribosome binding affect the final level of protein produced from a DNA sequence? determines the efficiency of transcription factor bindings determines how many proteins can be made from each mRNA determines mRNA stabiity determines teh rate of nuclear transport of mRNAS
Why might a DNA binding protein cause a protein to be toxic to the cell?
1. A biochemist is attempting to separate a DNA-binding protein (protein X) from other proteins in a solution. Only three other proteins (A, B, and C) are present. The proteins have the following properties: pl (isoelectric point) Size Mr Bind to DNA? protein A 7.4 protein B 3.8 protein C 7.9 protein X7.8 82,000 21,500 23,000 22,000 yes yes no yes What type of protein separation techniques might she use to protein X from the other proteins. Give a flow...
HP1 is a DNA binding protein that interacts with a specific
sequence (TGCTTATTC). You want to analyze, by a Dnase I
footprinting assay, the effect on DNA binding of the interaction
between HP1 and its 6 binding partner PA. In each assay, you
combine a radiolabeled fragment of DNA that binds to HP1 and a
specific combination of proteins. After incubation with DNase I,
each reaction mixture was resolved by gel electrophoresis, and then
exposed to film. The autoradiogram showing...
If the plasma protein binding of the drug cyclosporine increases, the volume of distribution of cyclosporine: Decreases C Increases C Show little change
Nucleosome positioning along the DNA can influence where transcriptional regulatory proteins are able to bind DNA. If a nucleosome is bound to an enhancer sequence, it may outcompete a regulatory protein from binding the same sequence. Conversely, if an enhancer sequence is in the linker DNA where the nucleosome is absent, the regulatory protein does not have to compete with the nucleosome. The position of the nucleosome can alter the accessibility of a sequence of DNA to DNA binding proteins....