Is Gene Therapy the Way Forward in Treating Genetic Diseases?

Gene therapy is a field of biology or medicine that focuses on introducing or replacing defective genes that are involved in the etiology of some genetic diseases.

To introduce or replace defective genes, this approach involves using viral or non-viral vectors to insert healthy copies of genes into the cells of affected people to re-establish their normal function within the targeted cells, tissues, and organs [1].

I. What is CRISPR Gene Editing?

Inserting healthy copies or correcting mutations genes rely on the use of genetic engineering techniques, such as the CRISPR gene editing method that can be specifically designed to recognize the defective gene, cut it at the desired location or replace it with a healthy and functional gene [2].

1- What Is Crispr?

Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences that are originally found in the genomes of microorganisms such as bacteria or archaea.

Because bacteria and archaea can be infected by a virus known as bacteriophage (phage), CRISPR sequences are used by bacteria and archaea to flank or tag the bacteriophage DNA that has been integrated into their genome by the bacteriophage.

CRISPR is used to quickly recognize and destroy the bacteriophage DNA that was inserted into their genome. Therefore, CRISPR is used as a form of acquired immunity for bacteria and archaea [3].

2- How Does Crispr Gene Editing Work?

When an infection by a bacteriophage happens, which involves the insertion of the bacteriophage DNA into the bacteria or archaea genome, bacteria or archaea produce an enzyme known as CAS9 (CRISPR-Associated protein 9) that recognize, cleave, and remove the CRISPR sequences that flank the bacteriophage DNA [3].

Therefore, the CRISPR/Cas9 technology can be used to specifically target defective or mutated genes within the cells of the human body by directing Cas9 directly to these genes are then recognized and cleaved by Cas9.

However, in the human body, Cas9 requires guidance towards the gene of interest to be cleaved.

In this case, the CRISPR/Cas9 technology uses specific RNA molecules known as RNA guides (gRNA) that contain the specific information about the gene of interest within the cells of the body and that will help Cas9 to recognize that specific gene and cleave it.

II. How Is Crispr Delivered in the Body?

Viruses or non-viral vectors are considered for the delivery of Cas9 and the gRNA in the cells of the body.

1- What Are Viral Vectors?

Viruses have the capacity to bind and introduce their genetic material to the host cells. Once the genetic material is introduced, new viruses are made using the infected cells by hijacking their ability to produce proteins.

Therefore, after making these viruses incapable of causing disease by removing some parts of their genetic material, these can be used to introduce Cas9 and gRNA to cleave and remove the gene of interest.

  • Retroviruses

Retroviruses are RNA viruses which means that their genome is not made of DNA but of RNA.

When these viruses enter the host cells and with the help of a viral enzyme known as transcriptase, they start making DNA copy from the RNA.

The newly generated viral DNA is then integrated into the host genome by another enzyme known as integrase.

Once integrated into the genome of the host cells, the viral DNA is transcribed in a similar way as the host DNA leading to the production of proteins and enzymes that help the multiplication of the virus.

Therefore, retroviruses can be used to introduce Cas9 and gRNA within the host cell which then go and recognize and cleave the gene of interest.

The advantage of using retroviruses for the delivery of Cas9 and gRNA is in their capacity to infect both dividing and non-dividing cells within the body as they can replicate their genes when the infected host cell is dividing.

  • Adenoviruses

Unlike retroviruses, adenoviruses are DNA viruses which means that their genome is made of DNA. Adenoviruses do not integrate their DNA in the host genome as they do not have an integrase.

This inability of integrating the DNA of the host, makes their replication limited as their genes are not replicated when the infected host cell is dividing.

Therefore, adenoviruses are best used for introducing Cas9 and gRNA in cells that do not divide, and therefore, are fully differentiated.

2- What Are Non-Viral Vectors?

Although the use of viruses for the delivery of Cas9 and gRNA into the host cells is an efficient method, they also have limitations such as immunogenicity of the host (immune response) and their production at large scales.

These limitations can be overcome through the use of non-viral vectors.

  • Injection of Naked DNA

Although the efficiency is limited, this method involves the injection of DNA into the muscles, which is then integrated by the cells.

  • Lipoplexes

Lipoplexes are liposomes that form complexes with nucleic acids, such as DNA and RNA, for delivery into the cells of the host. Because of their lipid nature, lipoplexes fuse with the cell membranes of the host cells and deliver their nucleic acids.

  • Polymersomes

Polymersomes are synthetic liposomes that also form complexes with nucleic acids for delivery to the host cells.

Nanoparticles are chemically synthesized or assembled products that have sizes that are within the nanometer ranges, and which include dendrimers, liposomes, metal nanoparticles, nanocrystals, nanosuspensions, polymer nanoparticles, block copolymer micelles, and polymer therapeutics.

Due to their small size, nanoparticles are used to form complexes with nucleic acids to ease their delivery to host cells.

  • Virosomes

Virosomes are made of liposomes that have nucleic acids (DNA, RNA) and viral proteins to facilitate their recognition and intake by the host cells.

III. Medical Applications of CRISPR Gene Editing

Gene therapy has been proposed for the treatment of several genetically related diseases, including cancer, hemophilia, cystic fibrosis, amyotrophic lateral sclerosis, age-related macular degeneration, sickle cell anemia, progeria, beta-thalassemia, Huntington disease, and Duchenne’s muscular dystrophy [1] [5].

However, so far, clinical trials to cure beta-thalassemia and sickle cell disease in human patients have shown promising results [4].


Although gene therapy is a promising medical approach, challenges regarding its efficacy, safety, and specificity must be further investigated before its use in clinics. Nonetheless, this therapy is highly fascinating and could provide significant hope in developing medical cures against deadly genetic diseases.

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