Science on Display, not just a Phage

Science on Display, not just a Phage

Rajini Rao’s post made me think of phage display libraries. Check out her post here:

The Enemy of My Enemy

https://plus.google.com/u/0/+RajiniRao/posts/LvxVPMLNyTV

What is a phage? A phage or more accurately a bacteriophage, is a virus that infects bacteria. You can read more about phages in Rajini’s post. Phage display libraries use phages to screen for peptides for diagnosis or treatment.

❈ What is a peptide?

Peptides are short chains (polymers) of amino acids. Think of peptides as the building blocks for proteins. So DNA gets translated into amino acids via mRNA, which make up peptides, which combine to make proteins. That’s an oversimplification but it’s easy to get the picture. 

You can read more here: http://goo.gl/aYzy7r

An example of two peptides are shown below.

❈ Phage display

George P. Smith at the University of Missouri developed phage display in 1985. He figured out that bacteriophages could be modified to incorporate “foreign” DNA and translate that to a peptide on their surface, hence the “display” aspect. After incorporating a DNA sequence into a phage, it can display the corresponding peptide on its surface. Why is that important and how can we take advantage of that? You can create a whole library of phages and see which phage has the best targeting for your particular model/system.

❈ Antibodies

You probably know that antibodies are part of the immune system and that they are specific for an antigen, e.g. bacterium. The thinking is that if you can make an antibody for say a particular tumor or protein involved with Alzheimer’s Disease, you could attach a therapeutic or diagnostic agent. Say you have such an antibody. You add a fluorescent component or radioactive element to make it diagnostic. Where ever the antibody binds, you will be able to image. Alternatively, say you take the antibody and add a drug so that the drug is now targeted. You can lower the dose because you don’t need to flood the whole body. So why doesn’t that really work? It has been tried. Antibodies are specific but have poor clearance and are bulky. When you have to add something to them, either a diagnostic or therapeutic component, it only gets more bulky, maybe too bulky to cross the blood brain barrier or too bulky to be cleared from the body in a reasonable time, so you end up with more side effects.

If you search Google Scholar for RGD (Arginine-Glycine-Aspartic acid) you’ll find over 50,000 hits. RGD is a peptide that’s associated with integrins. Integrins are cell surface receptors that are involved with cell signaling, for example in wound healing and cancer. Since a phage is smaller than an antibody, you can imagine that a phage display should be more effective than an antibody in terms of clearance, especially after adding a diagnostic or therapeutic agent as compared to an antibody.

❈ Radio labeled phage

Say you create a phage that presents a peptide that’s specific for a certain integrin. You add a radioisotope and test it against a tumor that has a lot of those integrins. That’s what’s shown in the picture below. A phage that was designed to bind with an alpha V beta 6 integrin with indium-111, which is a gamma radiation emitting isotope, was used in a mouse model with two tumor types. The tumor on the left side is negative for the alpha V beta 6 integrin and the right side is positive. You can see that the indium-111 labeled phage is accumulating on the right but not the left. The histogram shows the accumulation of radioactivity, i.e., labeled phage, for the positive vs. negative alpha V beta 6 tumors.

Sources:

Structural guided scaffold phage display libraries as a source of bio-therapeutics.

PLoS One. 2013 Aug 9;8(8):e70452.

http://goo.gl/Ky4D3l

Phage Display in Molecular Imaging and Diagnosis of Cancer

Chem. Rev., 2010, 110 (5), pp 3196–3211

Susan L. Deutscher

http://pubs.acs.org/doi/full/10.1021/cr900317f

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