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Print Posted on 05/15/2018 in Fertility Treatment Options

The Embryo Code Can Be Modified with CRISPR Technology for Genome Editing

The Embryo Code Can Be Modified with CRISPR Technology for Genome Editing

Genome Editing (or Gene Editing) are the technologies that give scientists the ability to alter the DNA strands’ structure. These technologies are used to correct the genetic defects or to exclude the possibility of the serious diseases’ further transmission to the baby. They allow genetic material to be EDITED, or, in simple words, to be added, removed, or altered at the particular locations in the genome.

(1) What is ‘Genetic Code’? Where is the genetic code hidden?

Virtually every tiny cell in your body contains the complete set of instructions for making you – YOU. These instructions are ENCRYPTED inside your DNA or the UNIQUE genetic code. Have you ever envisioned in your mind those tiny gorgeous DNA–curled spirals? DNA is a long, complex, ladder–shaped molecule that contains each person’s unique genetic code. And your UNIQUE genetic code is accurately designed, secretly encrypted, delicately enveloped and compactly packaged inside your DNA. 

DNA is so long molecule that it should be compactly packaged inside something and ‘ENVELOPED’. DNA molecules are so long that they can’t fit into the cells without the accurate and compact packaging. To fit inside cells, DNA is curled up tightly to form the special thread–shaped structures – the chromosomes. And the chromosomes are the bundles of tightly coiled DNA located within the nucleus. In other words, the chromosomes are the gorgeous envelopes for the DNA molecules. Each chromosome contains a single DNA molecule. Metaphorically saying, the DNA molecule curls itself up, twists itself up, cuddles itself up, twirls itself up inside the chromosome.

Or scientifically saying, a single length of DNA is wrapped many times around lots of proteins, called ‘histones’, to form structures called nucleosomes. These nucleosomes then curl up tightly to create chromatin loops. The chromatin loops are then wrapped around each other to make a full chromosome. Each chromosome has two short arms (p arms), two longer arms (q arms), and a centromere holding it all together at the centre. Each of us has 23 pairs of chromosomes, which are found inside the cell’s nucleus. The DNA making up each of our chromosomes contains thousands of genes. At the ends of each of our chromosomes are sections of DNA called ‘telomeres’. Telomeres protect the ends of the chromosomes during DNA replication.

(2) One AMUSING FACT about the genetic code

As we have mentioned, DNA is a long, ladder–shaped molecule, designed especially to encrypt your unique genetic code. Each rung on the ladder is made up of a pair of interlocking units. These called interlocking units are called bases. They are designated by the four letters in the DNA alphabet – ‘A’, ‘T’, ‘G’ and ‘C’. ‘A’ always pairs with ‘T’, and ‘G’ always pairs with ‘C’.

The most amusing fact about chromosomes: there are glittering chromosome tips at the ends of each chromosome (each chromosome tip has the sparkling molecular shoe on it). Isn’t it wonderful? Chromosomes do love the ought shoes couture. Therefore, there are so many glittering molecular shoes that are worn on every chromosome–tip. Sounds intriguing, isn’t it? These ‘shoes’ are called ‘telomeres’. Telomeres are the glittering chromosome–tips that prevent the gene loss. Every time a cell carries out DNA replication, the chromosomes are shortened by about 25–200 bases (‘A’, ‘C’, ‘G’, or ‘T’) per replication. However, ends of each of our chromosomes are protected by telomeres, the only part of the chromosome that is lost, is the telomere, and the DNA is left undamaged. Without telomeres, important DNA would be lost every time the cell divides. This would eventually lead to the loss of the entire gene. But it is safely encrypted, so you shouldn’t worry about that.

(3) What may happen with the DNA molecules?

When a cell divides in two, it makes a copy of its genome, then parcels out one copy to each of the two new cells without verifying the copies of the genome. So, two cells have the valid but different genome copies. Theoretically, the entire genome sequence is copied exactly. But in practice, a wrong base is incorporated into the DNA sequence every time a cell divides in two, or a base or two might be left out or added. These mistakes or DNA pattern alterations are called ‘mutations’. These mutations can cause many different diseases.

(4) What is CRISPR–Cas9 Complex/Platform and how does it work?

As the Embryo’s genetic code consists of the oocyte’s DNA (half of the mother’s genetic code) and spermatozoon’s DNA (half of the father’s genetic code), it should be edited after fertilization when the genetic code will be complete. That means that they will inject your embryos with the CRISPR–Cas9 Complex. And the injected CRISPR components that target and cut DNA in a specific place will EDIT [correct] the embryos’ genetic codes (disease–causing genetic mutations and mosaics). Especially CRISPR–Cas9 Platform is of essential to correct a mutation that causes an inheritable heart condition. Catching and correcting the mutation in this case, in the earliest stages of embryo development would either reduce or eliminate the need for treatment in the future.

The CRISPR–Cas9 Complex/Platform is an exceptionally accurate MOLECULAR tool for cutting DNA molecules at the specifically targeted locations. There are two molecular components in the CRISPR system: a DNA–cutting enzyme called Cas9, and another molecule known as a Guide–RNA. Cas9 enzyme cuts the genome at a site targeted by an RNA guide molecule. Bound together they form a complex/platform that can identify and cut specific sections of the DNA. Metaphorically, CRISPR–Cas9 Complex/Platform can be described as a molecular hand with wrists, palm, and fingers. Its molecular fingers are Cas9 DNA–cutting enzyme.

First, CRISPR–Cas9 complex identifies the disease–causing genetic mutations and mosaics in the DNA’s structure. After the identification, the CRISPR–Cas9 platform stops and Cas9 has to locate and bind to a common sequence in a genome (PAM gene (Protein Coding)). Once a PAM is bound, the Guide–RNA molecule unwinds the part of the double DNA’s Helix. The RNA–strand is exclusively designed to match and bind to a particular sequence in the DNA’s strand. It identifies the disease–causing genetic mutations and mosaics in those gorgeous DNA–curled spirals. Once it finds the correct sequence, enzyme Cas9 can cut the DNA’s strand. Cas9 has two nucleus domains ‘molecular scissors’ that cut a double DNA’s strand.

This technology works as a ‘tiny pair of molecular scissors’ that cut out the unnecessary DNA strand. Once the affected DNA is cut, the cell will repair the cut by joining the DNA strands’ ends (with some DNA at the cut side being lost so that a deletion is made), or by using any available DNA strands to complete the gap. Although the cell will try to repair this break, the fixing process often inevitably introduces the mutations that disable the defective gene.

(5) What else can CRISPR–Cas9 Complex/Platform do?

CRISPR–Cas9 Complex/Platform not only cuts out the defective genes. If one or both Cas9 cutting domains are deactivated, the new enzymes can be introduced to this platform. That seems that a ‘tiny pair of molecular scissors’ that cut out the unnecessary DNA strand will be deactivated, and the complex will work as a molecular platform that will transfer those new enzymes to a specific DNA’s sequence.

For example, the CRISPR–Cas9 Genome–Editing Complex/Platform can identify the defective DNA’s strand, which mutates the specific DNA–enzyme in the basis. Eventually, that enzyme can be replaced with the other enzyme. It is one of the most possible versions of exclusive Genome–Editing tools. It shows that it is possible to turn a disease–causing mutation into a healthy version of the gene.

The genetic code is a “blueprint” because it contains the instructions a cell requires to sustain itself. The instructions stored within DNA can be “read” in two steps: transcription and translation. In transcription, a portion of the double–stranded DNA template gives rise to a single–stranded RNA molecule. Transcription of an RNA molecule is followed by a translation step, which ultimately results in the production of a protein molecule. CRISPR–Cas9 Complex/Platform can be also used for the gene transcription and monitoring cell fate. They do it by deactivating Cas9 enzyme completely so that it can no longer cut DNA. Instead, the transcriptional activators are added to the Cas9 to activate (9) or repress gene expression.

(6) Are there any risks for the embryo? 

This genome–editing technology almost excludes the risk of making additional, unwanted genetic changes (called off–target mutations) and the risk of generating mosaics — in which different cells in the embryo contain different genetic sequences.

CONCLUSION:

Genome edition technologies are the interventions with the unique EDITING OPTIONS that can correct the known genetic defects by altering, removing or adding nucleotides to the genome. As a result, the DNA molecules are not only EDITED but also REPROGRAMMED. At present, the technique that is used for the embryo genome editing is called CRISPR–Cas9 Complex/Platform. This technique has shown the new sparkles in the genetics. Current scientific reviews show that CRISPR is not only an extremely versatile technology, it’s proving to be precise and increasingly safe to use. CRISPR allows editing the DNA sequences (to find, cut and then paste the new gene). Its many potential applications include identifying, validating and correcting the genetic defects, cutting the defected place in the DNA strands, treating and preventing the spread of diseases.

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