Sharmila

__**For Friday, 9/23:**__ References for table

18063294 15234240 12619114 21787266
 * 0. General Bacteria Homing Research**

__PMID__ 20029424 20857619 21925171 21277276 __LINKS:__ [] []
 * 1. Colorectal Cancer**

__PMID:__ 21947749 __LINKS:__ [] []
 * 2. Breast**

__PMID:__ 10767254 __LINKS:__ [] [] [] stanford.edu/~nikil/e145/OAP.do c
 * 3. HAC**

__**For Friday, 9/23:**__ - Looked in more depth at Human Artificial Chromosomes and TCR engineering - Studied technologies available through Tech Transfer office at Yale


 * 0. New research**



Here's a review that describes the use of bacteria to home to tumors.


 * 1. Further research on HAC and TCR engineering**

This is a review on progress made on Human Artificial Chromosomes so far. There are highlights in the article where I thought some of the more important points were. Key points from the review:
 * methods of gene transfer tried in the past have included adenoviruses and retroviruses containing parts of the genome, but problems with this are that they can sometimes mistakenly integrate the DNA into incorrect parts of the genome and "insertional mutagenesis" and that the expression is transient
 * the method being discussed here is the possibility of creating an artificial human chromosome, which is a microchromosome that can be up to 10 Mb in size and can function like a normal chromosome in that they are mitotically stable
 * researchers can engineer the chromosome to contain an entire genetic locus rather than a fragment of a desired gene
 * the potential therapy would be taking stem cells and getting them to take up the engineered chromosomes and then transplanting them into a patient to restore gene function
 * the method of chromosome uptake uses delivery through a microcell that fuses to the host cells. researchers are exploring new ways to improve this process
 * delivering an artificial chromosome to mice through ES cells has already been done by researchers
 * potential applications of have included treating Duchennes muscular dystrophy and using the mesenchymal cells homing system to introduce a suicide gene into tumor cells

I've attached some information on the use T Cell engineering to fight leukemia with a chimeric TCR, but this has received a lot of press recently, so that's something we should think about.


 * 2. Tech Transfer Office Information**

Some ideas from the tech transfer office
 * Cell specific siRNA delivery - this uses an oligonucleotide sequence that has a "targeting agent" linked to the siRNA which enables the siRNA to be internalized by the target cell.
 * Regulation of oncogenes by microRNAs - this is on a specific microRNA that can reduce RAS function to inhibit tumor formation. but this doesn't seem like something that could necessarily be applied outside this scope without more research into other specific miRNAs.
 * Method for inducing differentiation of blood monocytes to dendritic cells - this lab developed a way of turning monocytes into antigen presenting dendritic cells. I feel like unless we are somehow able to engineer the antigen they present, this might not be exactly what we're looking for.
 * transient transfection of cells with synthesized mRNA to create cytotoxic T cells that could potentially fight cancer or autoimmune diseases. This could also have applications to HIV or other viruses potentially.
 * Nanoparticle implementation - this lab was looking at ways to improve graft rejection outcomes, so they took immunosuppressive molecules and put them in nanoparticles in the graft tissue before transplantation. The nanoparticles are linked to the graft so they don't move around and they offer sustained release of immunosuppressive therapy. This might be something we could consider for other chronic diseases.
 * Peptide nucleic acids- sequences that can bind to specific sequences of DNA and effectively undergo recombination at those sites. These researchers used this technology to bind to the CCR5 gene and inactivate it so that HIV couldn't enter the genome, but there are other potential applications - could potentially knock out any gene
 * Artificial cellular antigen presenting cells - can be transfused ex vivo to be generate immunity against cancer, autoimmune disease, etc.

For Friday, 9/16 Looked through 2010 and 2011 archives for journals for cell transport, signal transduction, basic DNA research, and DNA repair. Also briefly looked through protein therapies and did some basic searches through pubmed.


 * __Key Papers__**



This is a pretty interesting idea for gene replacement therapies. People have already created artificial human chromosomes which can ectopically express genes. However, this paper describes the creation of a chromosome which has a centromere that can be conditionally activated or inactivated. The potential of this is that you could easily create negative controls when the gene of interest was not present, or you could transiently express genes.



The authors of this paper have engineered a T cell with a chimeric TCR that has specificity for tumors to be used for anti-tumor immunity. It uses something called nanobodies, which are "the smallest functional antigen-binding immunoglobulin fragments." We might be able to look into this a little more to see if we might be able to use the same technology for other diseases.



Protein transduction seems like something we might want to consider. So this paper uses lentiviral vectors to deliver proteins to a cell by fusing with the cell membrane and dumping their contents into the cell. There is no integration into the genome, so we would need to look a little more closely at how exactly transcription/translation happens. But this seems like it might be an interesting alternative to gene therapy. There is the issue of homing to specific cells though- that would need to be examined further as well.



This is more of an informational paper if we are thinking about doing something that relates to RNA. This paper uses neurons to understand how the cell moves mRNA around to localize translation of certain proteins to certain regions of the cell. We might be able to get some insights on sub-cellular (and potentially intracellular) homing and potential specifics about a disease.



New microarray technology that delivers more accurate RNA expression patterns at lower cost in shorter time. Could be used to improve diagnosis and understanding of risk factors for a wide variety of diseases. This is already a trademarked technology, but I thought it had the broad range of applications that we might be looking for, and might be a good example to keep in mind when searching.