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<p style="text-align: center;"><span style="font-size:18px"><strong>GWAS to therapy: Using GWAS data for therapeutics</strong></span></p>

<p style="text-align: right;">Joowon Yoon</p>

<p style="text-align: right;">School of Lifesciences, Ulsan National Institute of Science and Technology</p>

<p>Gene risk factor for disease can be detected by Genome-Wide Association Study (GWAS). Our goal is not just finding risk factors but . It is more important to use them in therapy. I studied 4 methods for use GWAS data to therapy- (1) Prevention, (2) Overlap between GWAS and known drug, (3) Finding new mechanisms of metabolic disease, (4) Gene therapy. I will suggest the future tasks for GWAS to therapeutics.</p>

<p>In the case of cancer, early detecting is very important for patient&rsquo;s survival rate. But However,&nbsp;it is difficult to detect if the cancer has no physiological trait in early stage. Understanding association of gene and trait could help early intervention or prevention of disease. For example, if someone has high risk factor of pancreatic cancer, he can have regular checkup to prevention and early diagnosis.</p>

<ol> <lip>(1)Gene therapy using an adenovirus vector.</li></olp>

<p style="margin-left:20.0pt">Using adenovirus vector, new gene can be inserted in patient&rsquo;s cell. It can transduce both non-diving and dividing cells. Carry up to 8Kbp heterologous DNA, and ensure high levels of transgene expression.</p>

<p style="margin-left:20.0pt">For example, assume that according to GWAS data, loss of copy number variants (CNVs) of gene A is related with disease D. D is related with loss of function. Inserting extra copy number of A can be helpful for treatment of D.</p>

<p style="margin-left:20.0pt">But However,&nbsp;this adenovirus vector has disadvantages. 1) It is highly immunogenic. 2) Vector genome does not integrate into the host genome, so it is not permanent therapy. 3) Hard to control expression levels 4) Hard to &ldquo;Knock-out&rdquo; host gene.</p>

<ol> <lip>(2) Gene therapy Using RNA interference.</li></olp>

<p style="margin-left:20.0pt">RNA interference (RNAi) is a biological process in which RNA molecules inhibit gene expression or translation by neutralizing targeted mRNA molecules. It can effectively silence specific target gene. In August 2018, FDA approved the first RNAi drug (Onpattro). RNAi can be used even if the mRNA is not translated to protein. If GWAS data gives a information about specific mRNA is associated with a disease, RNAi can inhibit it.</p>

<p style="margin-left:20.0pt">But However, RNAi is also not permanent, and hard to treat loss-of-function problem.</p>

<ol> <lip>(3) Gene editing using CRISPR/Cas9</li></olp>

<p style="margin-left:20.0pt">CRISPR (<u>C</u>lustered <u>R</u>egularly <u>I</u>nterspaced <u>S</u>hort <u>P</u>alindromic <u>R</u>epeats) / Cas9 (<u>C</u>RISPR- <u>as</u>sociated protein 9) is a unique technology that enables geneticists and medical researchers to edit parts of the genome by removing, adding or altering sections of the DNA sequence. It edits host genome, so therapy with CRISPR/Cas9 is permanent. Both &ldquo;Knock-out&rdquo; and &ldquo;Knock-in) are possible. It can edit specific loci. So, I think this gene editing is very powerful tool to adjust treatment from GWAS data.</p>

<p style="margin-left:20.0pt">But However, recent researches show CRISPR/Cas9 can make unexpected mutations, and also cause unwanted off-target effects.</p>

<p style="margin-left:20.0pt">We need to make safer the CRISPR/Cas9 system, or find next generation genome editing system for human gene therapy.</p>