The human genome encodes the instructions for all the
functions of living systems. It contains DNA sequences that determine the
physical and genetic characteristics of an organism. Genetic engineering is the
process by which an organism’s genome is altered in a particular way (1).
Advances in the field of genetic engineering allow for the examination of a
specific gene’s function by allowing the direct insertion, deletion, or
silencing of almost any gene in the human genome. The development of newer
techniques like the CRISPR (clustered regularly interspaced short palindromic
repeats system) has allowed more accurate and effective manipulation of target
genes (2). Genetic engineering can help provide a more precise understanding of
the complex mechanisms of human genetic diseases, can lead to more effective
treatments and diagnoses, and can create other genetic alterations that are
beneficial to human health.

The process of genetic engineering in humans has become
more efficient as technology advances. The time-consuming procedures of past
genetic engineering methods involved growing bacteria to produce a desired
protein that was later reinserted into an organism’s genome. A plasmid would
have to be designed with the DNA sequence of interest. The bacteria would then
need to be prepared to receive a transfection of the engineered plasmid. This
process was also expensive, time consuming and prone to errors (2). In
contrast, advanced methods of genetic engineering allows for the direct
manipulation of the genetic sequences in the human genome. The CRISPR system is
a universal system that can be used to target any site in the human genome; it
also uses a standardized protein and RNA sequence that works for any target
gene. The ease and efficiency of the CRISPR system in comparison to other
methods has allowed for the examination of the function of genes in diseases
(3).

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The CRISPR system is an advanced genetic engineering
technique that is precise and effective in editing any target in the human
genome. It is a universal system that can “cut” a specific gene and either
disrupt the genes function, or insert a new DNA sequence (4). This is different
from less advanced methods that can only partially eliminate a gene’s function.
 A complete gene knockout can more accurately describe the gene’s function
because one can examine the physical and biological effects on the organism.

Methods of advanced genetic engineering can be used to
completely alter the genetic makeup of human biology and can target diseases
like cancer. Cancer or other disease causing genes could be knocked out to halt
or eliminate the progression of the disease (2). Cancer cells exhibit many
mutations that help fuel their rapid growth. Similar mutations are seen in many
types of cancer and are known as the hallmark characteristics of cancer cells.
CRISPR can be used to attack cancer cells’ weaknesses by targeting their
prominent traits. One characteristic of cancer cells involves their metabolism.
Cancer cells exhibit altered metabolic rates that keep up with their demand for
cellular energy. Genes that are involved with producing cellular energy can be
knocked out to limit the cancer cell’s’ energy supply and consequently limit
cell growth and progression (5). Another characteristic of cancer cells is how
they avoid attacks from the body’s innate immune system. A specific gene
expressed on tumor cells codes for a protein that deters the immune system from
attacking it. The body’s innate immune system is not able to recognize the
mutated cancer cells as potential pathogens. The knockout of this immune
suppression gene using methods like CRISPR can allow the human immune system to
better recognize and control cancer. Using a similar concept, a patient’s
immune cells can be given mutations to help them better fight and recognize
cancer. Once the immune cells are edited, they can be reinserted back into the
patient to specifically target cancer cells and help keep the cells from
proliferating (6).

In
addition to improving the effectiveness of cancer treatments, genetic
engineering can help with curing disease caused by a few faulty genes. For
example, Cystic Fibrosis (CF) is caused by a mutation in the cystic fibrosis transmembrane conductance regulator
(CFTR) protein (7). Genetic engineering can be used to remove the faulty
sequence and reinsert the correct one. Huntington’s disease is also caused by a
specific gene mutation known as the mutant version of the Huntingtin gene (mHTT).
The correction of this faulty gene could permanently eliminate the brain
poisoning caused by Huntington’s (8).

Along with the capabilities of genetic engineering to
help cure and prevent diseases, genetic engineering can also be used for patient
recovery. CRISPR could be used to repair a damaged heart after a heart attack
by activating the gene that regenerates heart muscle tissue (9). In a similar
manner, CRISPR could be used to regenerate cartilage tissue in joints and
prevent chronic inflammation. Genetically engineered cells are given a gene
that can fight inflammation (10).

The information about chronic inflammation and patient
recovery may not be completely reliable because the sources used are not
supported by scientific evidence and are more opinion based. The sources are
hypothetical and possibly prone to bias, but provide different perspectives on
advanced genetic engineering in humans. The other sources used are peer
reviewed and are credible sources that have multiple references.

In addition to creating genetic alterations in humans,
genetic engineering is being used to reduce infectious diseases spread by
mosquitoes. Gene drives are used to control mosquito populations and give the
mosquitoes mutations that create genes resistant to disease. For example,
mosquitoes carrying malaria can be given a specific gene that is resistant to
the malaria pathogen. CRISPR can be used to engineer gene drives that ensure
the mosquitoes carry on their resistant genes through each generation (11).

Advanced
genetic engineering can be used to correct mutated genes and introduce new
genetic sequences, but off-target mutations can cause unintended consequences. Because
the human composed of many different sequences, the CRISPR system can cleave an
off-target DNA sequence that may differ by a few nucleotides from the intended
target. Off-target effects can cause genomic instability and can disrupt the
function of normal genes (12). The mutations that are the consequences of
off-target effects can have potentially harmful effects on humans. Off-target
effects could activate a gene involved in the progression of a specific
disease. To reduce off-target effects, algorithms are being developed to select
sequences with a lower chance of gene variability.

Advanced
genetic engineering helps with the understanding of the complex human genome, the
mechanisms by which genetic diseases progress, and with the alteration of human
characteristics. The precision and accuracy of newer methods has allowed for
the examination of the mutated genes that cause cancer and other genetic
diseases. In addition to halting the progression of genetic diseases, genetic
engineering can be used for controlling infectious disease rates and recovery
rates in humans. Precise alterations of the human genome using advanced genetic
engineering methods are advancing medical treatments, diagnostics, and the
genetic foundation of human biology.

 

 Word Count: 1159

 

Citations

1.   CRISPR: A game-changing genetic engineering
technique. (2014, July 31). Retrieved October 16, 2017, from
http://sitn.hms.harvard.edu/flash/2014/crispr-a-game-changing-genetic-engineering-technique/.

2.   Gaj, T., Gersbach, C. A., & Barbas,
C. F. (2013). ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends
in Biotechnology, 31(7), 397-405. doi:10.1016/j.tibtech.2013.04.004.

3.  Genetic
Modification, Genome Editing, and CRISPR. (n.d.). Retrieved October 15, 2017,
from
https://pged.org/genetic-modification-genome-editing-and-crispr/.

4.     CRISPR/Cas9
Plasmids and Resources. (n.d.). Retrieved October 28, 2017, from https://www.addgene.org/crispr/.

5.
    Cancer Cell Metabolism. (n.d.). Retrieved November 22,
2017, from
https://nutritionaloncology.org/cancerCellMetabolism.html.

6.     T-Lymphocytes
– National Library of Medicine – PubMed Health. (n.d.). Retrieved October 28,
2017, from
https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0022044/.

7    Precise
treatment of cystic fibrosis – current treatments and perspectives for using
CRISPR. (n.d.). Retrieved November 22, 2017, from
http://www.tandfonline.com/doi/full/10.1080/23808993.2016.1146077.

8.
     Yang, S., Chang, R., Yang, H., Zhao, T., Hong,
Y., Kong, H. E., . . . Li, X. (2017, June 30). CRISPR/Cas9-mediated gene
editing ameliorates neurotoxicity in mouse model of Huntington’s disease.
Retrieved November 22, 2017, from
https://www.jci.org/articles/view/92087.

9.  “Cardiac
regeneration in vivo: Mending the heart from within?” Stem Cell Research,
Elsevier, 16 July 2014,
www.sciencedirect.com/science/article/pii/S187350611400083X.

10.
  Mayer, K. (2017, April 28). CRISPR-SMART Cells Regenerate
Cartilage, Secrete Anti-Arthritis Drug. Retrieved November 22, 2017, from
https://www.genengnews.com/gen-news-highlights/crispr-smart-cells-regenerate-cartilage-secrete-anti-arthritis-drug/81254274.

11. “Gene drive’
mosquitoes engineered to fight malaria.” Nature News, Nature Publishing
Group,
www.nature.com/news/gene-drive-mosquitoes-engineered-to-fight-malaria-1.18858.

12.  Off-target
Effects in CRISPR/Cas9-mediated Genome Engineering. (2016, December 14).
Retrieved October 28, 2017, from
http://www.sciencedirect.com/science/article/pii/S216225311630049X.

 

 

 

 

 

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