I am a new member of OpenWetWare!
- John Chen
- Massachusetts Institute of Technology
- 229 Vassar St.
- Cambridge, MA 02139
- johnchen AT mit DOT edu
I learned about OpenWetWare from my 20.109 academic instructor, and I've joined because of academic/class materials.
- 2013, BS, Massachusetts Institute of Technology
- Aptamers are molecules that bind to a specific target molecule
- Through the process of SELEX (Systematic Evolution of Ligands by Exponential Enrichment), one can isolate and enrich aptamers that are specific for the particular target in question
- This has applications in research such as sorting through a patient's blood sample to find particular cancer cells (1. Xu, Ye. "Aptamer-Based Microfluidic Device for Enrichment, Sorting, and Detection of Multiple Cancer Cells." Anal. Chem.. (2009): 7436-7442. Print)
- Other applications include the use of aptamer-derived particles for treatment of HIV, cancer and other diseases by targeting specific target molecules
- Our goal is to, by understanding the binding kinetics of many cellular processes such as transcription and translation, create a method for the in vivo production of these aptamers to combat these diseases (as opposed to simply for diagnostic purposes or ex vivo injection)
Ideas and approaches
- Design a method to self-produce aptamers to combat undesired blood clotting or blood clotting diseases (such as hemophilia)
- Design a way to self-produce aptamers to combat metabolic processes in individuals with certain enzymatic deficiencies
- Engineer a way to endogenously produce aptamers that prevent prostate cancer cells
- Using principles of synthetic biology, engineer a ways to use the bacteria living in the human body to produce aptamers/chemicals in response to a particular deficiency or disease (HIV, metabolic diseases, etc)
Review of the literature
DNA Aptamers Binding to Multiple Prevalent M-Types of Streptococcus pyogenes This study describes using SELEX to isolate aptamers that are specific for several types of Streptococcus pyogenes, which are bacteria that cause diseases such as strep throat. Results showed that they bind preferentially to the specific strains in question in much higher affinity than to other bacteria. This research can potentially aid in the detection of strep throat and other diseases that are caused by these strains of bacteria. Hamula, Camille. "DNA Aptamers Binding to Multiple Prevalent M-Types of Streptococcus pyogenes." American Chemical Society (2011): A-H. Web. 25 Apr 2011. <http://www.ncbi.nlm.nih.gov/pubmed/21504182>.
Preventing the growth of prostate cancer cells through aptamers This study describes the development of aptamers that bind specifically to Androgen Receptors (AR), whose activity repression is essential to controlling the proliferation of prostate cancer cells. The aptamer was designed such that it bound specifically to the AR and also had another domain that served to silence the target gene of the AR. Transport of the aptamer was made without a vector by binding this corepressor to a protein transduction domain (PTD). Reeb, CA. "A Designed Cell-Permeable Aptamer-Based Corepressor Peptide Is Highly Specific for the Androgen Receptor and Inhibits Prostate Cancer Cell Growth in a Vector-Free Mode.." Endocrinology (2011): http://www.ncbi.nlm.nih.gov/pubmed/21486935. Web. 18 Apr 2011. <http://www.ncbi.nlm.nih.gov/pubmed/21486935>.
Combatting HIV by Aptamers and siRNAs
This study describes using aptamers and siRNAs (small interfering RNAs) as a potential way of HIV and AIDS treatment. An aptamer-siRNA dual system is used in which both components contribute to the prevention of HIV proliferation. A glycoprotein on the surface of HIV is important in the infection process by targeting and integrating into CD4 T cells. These aptamers target the glycoprotein, and the Dicer substrate siRNA delivered by these aptamers inhibit HIV proliferation and infection.
Zhou, J. "Aptamer-Targeted RNAi for HIV-1 Therapy.." Methods in Molecular Biology (2011): 355-71. Web. 17 Apr 2011. <http://www.ncbi.nlm.nih.gov/pubmed/21431697>.
Coupling carbon nanotubes with aptamers for drug delivery This study takes the application of single-wall carbon nanotubes (SWNTs) for drug delivery and extends it to aptamers as well. In this study, leukemia cell aptamers that also complex with the nanotubes as well as the Dau drug are investigated to see its efficacy of delivering Dau to the leukemia cells. The release of Dau was found to be largely correlated to pH changes, and the delivery of the drug was quite selective, as internalization in the leukemia cells was highly efficient while not so in non-target cells. Taghdisi, SM. "Reversible targeting and controlled release delivery of daunorubicin to cancer cells by aptamer-wrapped carbon nanotubes." Eur J Pharm Biopharm (2011): 200-06. Web. 18 Apr 2011. <http://www.ncbi.nlm.nih.gov/pubmed/21168488>.
Understanding RNA-protein interactions in processes such as translation and transcription through the use of aptamers
Many processes involving the interaction between RNA and protein are not well understood. This study describes the use of tethering RNA to tRNA to pull out transcript-specific RNA-binding proteins. The Streptavidin aptamer increased binding efficiency about 10fold. Proteins that bind specifically to introns or UTRs were all pulled out by such aptamers. This process is potentially useful in understanding many RNA-protein interactions in genes of many different functions or of many different organisms.
Iloka , H. "Efficient detection of RNA-protein interactions using tethered RNAs." Nucleic Acid Res (2011): n. pag. Web. 18 Apr 2011. <http://www.ncbi.nlm.nih.gov/pubmed/21300640>.