1. Curing Werner’s Syndrome Using CRISPR-CAS
Tianna Bailey and Keara Coffield, Department of Biological Sciences, Hampton University
Statement: A Feasibility Study
Identification and Historical Observation of Werner’s Syndrome as a Genetic
Disorder
Throughout the history of biology, medicine, and genetics there has been many puzzling
questions on particular genetic disorders. Otto Werner in 1903, for example discovered a
disease known as “Werner’s Syndrome” or adult progeria which causes premature aging
at a very young age. By using observations and experiments on families, he noticed that
this disease caused people as young as the age 20 develop cataracts and appear to
have old and wrinkly faces. Also, he discovered that they usually die around their early
50’s. In 1996, it became apparent that this disease was caused by a genetic mutation on
an WRN gene on Chromosome 8. Currently this disease is often found in Japan due to
the inbreeding with family members. It has a very rare occurrence in the United States.
What Type of Illnesses and Diseases do Individuals with Werner’s Syndrome
Endure?
Usually people with this rare, autosomal recessive gene linked disorder have problems
with their internal organs such as cardiac arrest, sexual organ reproduction, clogged
arteries of muscles, and trouble with their skin and eyesight. Also, there are changes in
their voice which becomes very hoarse, and they appear to have “bird-like” faces. Also if
a person is diagnosed with this disease, is high risk for rare types of cancer like
sarcoma(cancer of the bones) and melanoma (cancer of the skin).
What is Used Currently to Detect This Genetic Disorder?
Currently, scientists are trying to find a treatment for this disorder, however the only way
to prevent it from happening is through testing. One of the methods of testing is used to
measure the levels of hyaluronic acid in the urine. The higher the levels of hyaluronic
acid in the patients urine, the more likely they will be considered to have this disease.
How Will This Disease be Prevented by Using CRISPR-CAS Technology?
CRISPR-CAS technology recently has been one of the most new and popular DNA
editing tools to be able to electronically fix abnormal DNA. Since Werner’s Syndrome is a
disorder caused by a mutation, a stop codon is erased and a new DNA segment is
created to repair the “Werner’s Syndrome” DNA and transform it into a “normal aging”
DNA sequence.
Key Questions Involving Werner’s
Syndrome
Materials
Procedure
Data / Observations Using CRISPR-CAS
Motivation for this Project
Conclusion
• .
CRISPR CAS made it possible to delete a specific part of the genetic code in
Werner’s syndrome that created a stop codon. The stop codon in the DNA
sequence was replaced with nucleotide sequences that made it possible for
“normal aging” to occur. Without the technology of CRISPR-CAS, Werner’s
Syndrome would be difficult to change
Works Cited
• "JNCI J Natl Cancer Inst." Werner's Syndrome: What Does An Aging Syndrome Gene
Reveal About Cancer? N.p., n.d. Web. 31 Mar. 2015.
<http://jnci.oxfordjournals.org/content/91/7/589.full>.
• "Vitamin C 'cures' Mice with Accelerated Aging Disease." ScienceDaily. ScienceDaily, n.d.
Web. 31 Mar. 2015. <http://www.sciencedaily.com/releases/2010/01/100104101210.htm>.
• "Werner Syndrome." Cancer.Net. N.p., 25 June 2012. Web. 31 Mar. 2015.
<http://www.cancer.net/cancer-types/werner-syndrome>.
• "Werner Syndrome." Genetics Home Reference. N.p., n.d. Web. 31 Mar. 2015.
<http://ghr.nlm.nih.gov/condition/werner-syndrome>.
• "Werner's Syndrome." Whonamedit -. N.p., n.d. Web. 31 Mar. 2015.
<http://www.whonamedit.com/synd.cfm/892.html>.
• "WRN Gene." Genetics Home Reference. N.p., n.d. Web. 31 Mar. 2015.
<http://ghr.nlm.nih.gov/gene/WRN>.
• Werner’s Syndrome is a rare condition but also lead to some deadly diseases. Werner’s
Syndrome only affects 1 in 200,000 people in the United States. Even though this is such
a small number, Werner’s Syndrome is one disease that can be fixed, in which it could
extend the life expectancy of a person. People who are affected by Werner’s Syndrome
can end up getting cancer, osteoporosis and atherosclerosis (hardening of the arteries)
which are common ways of death with people with this syndrome. By using CRISPR CAS,
altering the genetic sequence makes targeting this syndrome easier in which people will
not have to suffer through this syndrome.
• Be able to help individuals in Japan with the disorder since it is most common in that area.
• Stop a younger person from premature aging and also deal with other complicated issues
like cancer when this disorder is inherited.
What to Look Forward To Over the
Years With Werner’s Syndrome
•CRISPR CAS
•Nucleotide sequence
Werner’s Syndrome occurs through a mutation that presents a stop codon when a DNA sequence is
transcribed. To prevent the stop codon from forming, the use of CRISPR-CAS will be used to delete the
DNA sequence in which the Stop Codon is formed, and change the nucleotide sequence, so “normal
aging” will result when the DNA sequence is transcribed.
Template 5’AGAATAATG GCC CCC AAA CAT GTT CTC ATC CTG AGA TTG ACAAAAAGG AAG CAG CGA CTC TAG AAG
GCAACAAGG CCA GCA GCG AGG CTA GGG TTC TAG AAC GAT3’
Replication 5’TCT TAT TAC CGG GGG TTT GTA CAA GAG TAG GAC TCT AAC TGT TTT TCC TTC GTC GCT GAG ATC TTC
CGT TGT TCC GGT CGT CGC TCC GAT CCC AAG ATC TTG CTA3’
RNA 5’AGAAUAAUG GCC CCC AAA CAU GUU CUC AUC CUG AGA UUG ACAAAAAGG AAG CAG CGA CUC UAG AAG
GCAACAAGG CCA GCA GCG AGG CUA GGG UUC UAG AAC GAU3’
By using CRISPR CAS to erase the stop codon, and adding a new sequence so “normal aging” occurs.
Template 5’AGAATAATG GCC CCC AAA CAT GTT CTC ATC CTG AGA TTG ACAAAAAGG AAG CAG CGA CTC TAG AAG
GCAACAAGG CCA GCA GCG AGG CTA GGG TTC TAG AAC GAT3’
Replication 5’TCT TAT TAC CGG GGG TTT GTA CAA GAG TAG GAC TCT AAC TGT TTT TCC TTC GTC GCT GAG ATC TTC
CGT TGT TCC GGT CGT CGC TCC GAT CCC AAG ATC TTG CTA3’
RNA 5’AGAAUAAUG GCC CCC AAA CAU GUU CUC AUC CUG AGA UUG ACAAAAAGG AAG CAG CGA CUC UAG AAG
GCAACAAGG CCA GCA GCG AGG CUA GGG UUC UAG AAC GAU3’
The stop codon is erased.
Template 5’AGAATAATG GCC CCC AAA CAT GTT CTC ATC CTG AGA TTG ACAAAAAGG AAG CAG CGA CTC TAG AAG
GCAACAAGG CCA GCA GCG AGG CTA GGG TTC CGA AAC GAT3’
Replication 5’TCT TAT TAC CGG GGG TTT GTA CAA GAG TAG GAC TCT AAC TGT TTT TCC TTC GTC GCT GAG ATC TTC
CGT TGT TCC GGT CGT CGC TCC GAT CCC AAG GCT TTG CTA 3’
RNA 5’AGAAUAAUG GCC CCC AAA CAU GUU CUC AUC CUG AGA UUG ACAAAAAGG AAG CAG CGA CUC UAG AAG
GCAACAAGG CCA GCA GCG AGG CUA GGG UUC CGAAAC GAU3’
A new sequence is shown and allowing a normal aging process to begin.
• How does Werner’s Syndrome cause rare types of cancer? Werner’s Syndrome can
cause many types of rare cancer by affecting the blood and muscular tissue that
appears to be abnormal and showing signs of cancer.
• How can CRISPR CAS gene editing technology help to alter the DNA sequence to
promote normal aging? CRISPR-CAS technology can stop the disorder from
occurring by deleting the mutation and transcribing a new DNA sequence.
• Why does it happen mostly in Japan? Many people in Japan inherit the disorder
mostly because of inbreeding and incest that happens in family households.
Werner’s Syndrome
BIO 408 & 505 Biology
Research Class Research
Project
Spring, 2015