JOHN ALEXIS E.

CALVERO
JOHN CHELL ANN P. MACARAEG
GENERAL BILOGY 2

BREAKTHROUGHS IN GENETIC ENGINEERING

Genetic engineering ‘breakthrough’ could slow aging, reverse blindness

In what is said to be a breakthrough for genetic engineering, scientists have restored sight in partially-
blind rats by using a new technique that may even extend the human lifespan.

Researchers at the Salk Institute in San Diego, California, have uncovered what they have described as
the “holy grail” in genetic editing – how to insert new strands of DNA into non-dividing cells such as
those in the brain, heart, and liver. 

The successful experiments were performed on rats suffering from retinitis pigmentosa, an eye
condition causing blindness that also affects one in 4,000 humans. After a few weeks, tests showed that
the rats were able to respond to light.

“We were able to improve the vision of these blind rats,” researcher Reyna Hernandez-Benitez said in a
statement published on the Salk website. “This early success suggests that this technology is very
promising.”

This new gene editing technique, dubbed HITI or homology-independent targeted integration, is based
on an earlier method known as the CRISPR-Cas9 system. The scientists hope that HITI will be able to
treat previously incurable retinal, heart, and neurological diseases.

“We are very excited by the technology we discovered because it’s something that could not be done
before,” said fellow researcher, Professor Juan Carlos Izpisua Belmonte. “For the first time, we can
enter into cells that do not divide and modify the DNA at will. The possible applications of this
discovery are vast.”

The scientific community has been abuzz with excitement at the discovery, and some have even
speculated that it could be used to slow down ageing.

“Researchers are now using this mechanism to correct gene defects,”  Professor Robert MacLaren,
Professor of Ophthalmology at the University of Oxford, told the Science Media Centre. 

“Clinical trials are a long way off because the CRISPR proteins may cut DNA at other sites that may
have untoward effects. Nevertheless, since ageing is defined as picking up DNA mutations, the ability
to correct these mutations may in future provide us with a means of extending our lifespan as well as
treating many diseases that relate to ageing.”
Others have been more reserved in their praise.

“As reported, the methods are not super-efficient,” said Professor Robin Lovell-Badge of The Francis
Crick Institute.  “However, with improvements in this type of technology, which seem inevitable these
days, it is likely that the methods developed here could prove to be a very useful way of adding genes
to non-diving cells, certainly for purposes of basic research, and perhaps eventually for gene therapy
to treat otherwise incurable diseases,” he continued.

“It is a complicated paper, and it does not quite reach the level as hyped in the press release, but it is
indeed rather important,” the professor noted.

Injecting blood from young people into old mice improves the mice’s brain power and leads to increased
physical activity, according to new research. The finding could lead to breakthroughs for people
suffering from degenerative conditions such as Alzheimer’s Disease.

The findings, which have yet to be peer-reviewed, were presented at the Society for
Neuroscience annual meeting in San Diego, California on Monday, the New Scientist reports.

Researchers from anti-ageing research company Alkahest took blood samples from 18-year-old humans
and injected the plasma into 12-month-old mice twice a week for three weeks.

A one-year-old mouse is roughly equivalent to a 50-year-old human, and by that age mice have already
started to show signs of ageing such as deteriorating memory and being less physically active.

When injected with human plasma, the old mice began to behave like younger mice, running around in
open spaces. Their memory also showed improvements when tested in a special maze that measures
spatial learning and memory.

The elixir of youth appears to be in the blood plasma. A previous study had involved surgically conjoining
young mice with old mice so that they shared a blood supply for several weeks. Older mice received the
younger one’s blood and vice versa.

Old mice that received young blood experienced a boom in the growth of brain cells in the
hippocampus, a part of the brain that plays a key role in memory. Meanwhile, receiving old blood had
the opposite effect on the brains of young mice.

When researchers at Alkahest examined the effect on the mice’s brains after receiving human blood
they also found evidence of new cells being created in the hippocampus.

The team believes that the young plasma appears to be the key factor in reversing the effects of ageing
and says their method has the potential to be developed into a treatment for human patients. A trial is
already underway with people suffering from Alzheimer’s.

“There’s anecdotal evidence that people experience benefits after blood transfusions,”  Sakura
Minami, a neuroscientist with the company, told New Scientist.
 Scientists have successfully corrected a severe disease-causing gene mutation in healthy,
viable human embryos for the first time.

The field of genetic engineering passed a major milestone this August. According to an article published
in Nature, scientists have successfully corrected a severe disease-causing gene mutation in healthy,
viable human embryos for the first time.

Our genetic code is the fundamental properties of what makes up each and every one of us and what
makes us an individual. Our genes are pieces of the code that order everything in the cell what to do and
sometimes there are errors in the code that can cause problems and disease such as cancer, blindness,
or cystic fibrosis. Inherited errors in the code from either parent have been the hardest to fix thus far.

Scientists announced in August that they had used CRISPR technology in human embryos to repair a
mutation linked to hypertrophic cardiomyopathy, which can cause sudden death. This achievement has
implications for a range of devastating genetic conditions.

CRISPR, or Clustered Regularly Interspaced Short Palindromic Repeats, which alludes to the structure of
code, is a revolutionary technology used in many areas of science to edit the genetic code of an
individual. Its interdisciplinary origins come from the pioneering biochemist Jennifer Doudna and her
microbiology counterpart, Emmanuelle Charpentier. Interestingly however, the patent on the
technology is hotly debated as Feng Zhang and his laboratories lay claim to CRISPR technologies as well.

Nonetheless, it was Doudna and Charpentier that examined the potential of the bacterial gene-enzyme
duo, CRISPR-Cas9. In essence, CRISPR is a gene in bacteria that recognises a viral attack and tells the
Cas9 protein to essentially snip out some of the viral DNA and record it in its own DNA, creating a sort of
library of past disease to repel possible future attacks. It is this snipping ability that was of interest to the
intrigued scientists.

Although a long way from clinical use, this research is monumental and may pave the way for the use of
gene editing in protecting babies from a variety of hereditary conditions. However, there has been a lot
of speculation that this feat of human genetic engineering may also lead to eugenic ‘designer baby’
traits such as higher intelligence, more creativity, or greater athleticism.

An ethical quandary often ensues when discussing the consequences of making inherited changes to
human DNA. If this technology is allowed to flourish uninhibited, could it lead to a major disparity
between those with means being able to mail order designer babies and those born with disabilities
being devalued? Ok, we’ll hold off on the Charlie Brooker dystopia just for now, but with currently only
being on the frontier of this novel technology, who’s to say what possibilities are out there.
The study, published in Nature, comes hot of the heels of an American National Academy of Sciences,
Engineering and Medicine committee convened to advise guidelines for modifying embryos. While some
scientists called for a complete blanket ban on research involving human embryos and the editing of
their DNA, a restricted approach was welcomed with the committee endorsing only alterations to genes
known to cause “serious diseases and disability” and only if in a situation with “no reasonable
alternative.” These stringent and explicit guidelines make it very difficult for any genetic research to be
performed in the US, leaving it to countries like China, South Korea, and Sweden.

In this study, scientists at the flagship Oregon Health and Science University, along with colleagues in
California, China and South Korea, reported that they repaired a mutation that causes a common heart
condition in dozens of embryos.

If these embryos with the repaired mutation could develop into babies they would be free of the disease
and free from passing it on to any descendants. The key to this study was that the embryos made were
disease-free in all of their cells, with previous efforts only applying the change in some cells. Of course,
this research is still in its infancy and is nowhere near ready for clinical trials. However, if the technology
can be proven to be safe and prevent other mutations, it has the potential of helping out couples that
cannot have healthy children. There are over 10,000 diseases caused by specific inherited traits
including breast and ovarian cancers, cystic fibrosis, Tay Sach’s disease, and some early onset
Alzheimer’s cases. Ireland has one of the highest per capita amount od cases of cystic fibrosis, caused by
an error in the CFTR gene, and this technology could help couples who are carriers of the gene have
healthy, CF-free babies. Genetic screening to identify mutations in embryos is already common among
couples undergoing in vitro fertilization. Another ethical issue arose surrounding prenatal screening in
Iceland, with close to 100% of parents whose embryos tested positive for Down’s Syndrome choosing to
abort.

In any case, fertility specialists one day may be able to offer the option to repair the DNA of an embryo
instead of discarding it if a mutation is found. Right now the procedure is only experimental and the
embryos that were used in the study published were destroyed after three days.

Outside of the ethics debate, the research did reveal one exciting new discovery on how embryos repair
themselves. Usually, genes that copy a DNA template introduced by scientists carry out the editing
process. In these embryos, the sperm cell’s mutant gene ignored that template and instead copied the
healthy DNA sequence from the egg cell.  The mutated gene in question is the MYBPC3 gene, which can
cause hypertrophic cardiomyopathy, a disease affecting about 1 in 500 people. If one of the parents has
an affected gene, there is a 1 in 2 chance of a child receiving it. Sperm from an affected male fertilized
twelve eggs from healthy women. After CRISPR-cas-9 was injected into the sperm, it acts as a scissors
snipping out mutated sequence of DNA from the male gene.

The researchers injected a healthy template DNA sequence in the fertilized egg, hoping it would copy
the template sequence into the cut section. Instead, the male gene copied the healthy sequence from
the female sequence, which was surprising and interesting as we do not know and can only speculate
why this happened. Perhaps it’s an evolutionary response to growth and development. It is currently
thought that the same process should occur for disease-causing mutations on maternal genes by
copying the healthy paternal genes. The technique would not work, however, if both paternal and
maternal genes were mutated. The new research although raising ethical concerns, has shown new
insight into infertility and miscarriage, something that affects many people. Whichever side of the fence
you lie, it’s clear to see that we are on the verge of something great.

CRISPR offers an easy, exact way to alter genes to create traits such as disease resistance and
drought tolerance.

A new gene-editing method is providing a precise way to modify crops in hopes of making them yield
more food and resist drought and disease more effectively. Research in the past year has shown that the
resulting plants have no traces of foreign DNA, making it possible that they will not fall under existing
regulations governing genetically modified organisms and will sidestep many of the consumer concerns
over these GMOs.

The technology is known as CRISPR,  and plants modified with it are sprouting in laboratory greenhouses
around the world. Already, a lab in China has used it to create a fungus--resistant wheat; several groups
in China are using the technique on rice in efforts to boost yields; and a group in the U.K. has used it to
tweak a gene in barley that helps govern seed germination, which could aid efforts to produce drought-
resistant varieties. Indeed, because it’s so easy to do and the plants could avoid the lengthy and
expensive regulatory process associated with GMOs, the method is increasingly being used by research
labs, small companies, and public plant breeders unwilling to take on the expense and risks of
conventional genetic engineering.

The gene-editing technique could be critical in helping scientists keep up with the constantly evolving
microbes that attack crops, says Sophien Kamoun, who leads a research group at the Sainsbury Lab in
Norwich, England, that is applying the technology to potatoes, tomatoes, and other crops to fight fungal
diseases. “It takes millions of dollars and many years of work to go through the regulatory process,”
Kamoun says. “But the pathogens don’t sit and wait for you; they keep evolving and changing.”

A version of CRISPR he co-developed paved the way for recent work on barley and a broccoli-like plant
at the John Innes Centre, a plant science research center also in Norwich. Kamoun and colleagues
showed that the second generation of some of the edited plants contain none of the foreign DNA that
had been used to create the first generation. (Though CRISPR doesn’t require inserting foreign genes, it
does typically use bits of bacterial genetic material to target the editing.) Meanwhile, a group at Seoul
National University has avoided leaving any foreign genetic material even in first-generation plants.

Big and small companies alike are jumping in. DuPont Pioneer has already invested in Caribou
Biosciences, the CRISPR startup cofounded by Jennifer Doudna, one of the inventors of the technology,
and is using it in experiments on corn, soybeans, wheat, and rice. It hopes to sell seeds bred with CRISPR
technology in as little as five years.

The big question is whether CRISPR crops will be governed by the same regulations as GMOs. The U.S.
Department of Agriculture has already said some examples of gene-edited corn, potatoes, and soybeans
(edited using a different method, known as TALENs) don’t fall under existing regulations. But both the
United States and the more restrictive European Union are now conducting reviews of today’s
regulations. And Chinese authorities have not said whether they will allow the crops to be planted.