Understanding Gene Therapy

Gene therapy involves identifying the gene(s) responsible for a disorder, making copies of the normal gene, inserting the copies into vectors, infecting the affected cells with the vectors, and activating the gene for transcription and translation.

Viruses are commonly used as vectors in gene therapy due to their ability to insert DNA into host cells.

Four different types of viruses are used in gene therapy: Adenovirus, Adeno-Associated Virus (AAV), Retrovirus, and Herpes Simplex Virus (HSV).

Each virus type has its advantages and disadvantages: Adenovirus infects many cell types but does not integrate into the host genome and can be lost; Retrovirus integrates into the host genome and cannot be lost but can cause cancer; AAV integrates into the host genome and cannot be lost but is difficult to work with; HSV keeps the DNA in the nucleus without integrating but only infects cells of the nervous system.

Gene therapy has had disappointments in the past, including a boy's death due to an immune response to an adenovirus gene therapy vector in 1999 and four children developing cancer from a retrovirus gene therapy vector.

Successes in gene therapy include treatments for several inherited immune deficiencies, such as Severe Combined Immune Deficiency (SCID), Adenosine deaminase (ADA) deficiency, and hereditary blindness. In some trials, vision loss was slowed or even reversed for a few years.

Gene therapy is also being used to treat other conditions, such as hemophilia, where a small trial successfully used an adeno-associated viral vector to deliver a gene for Factor IX to liver cells.

In 2007, a patient received successful gene therapy for severe beta-Thalassemia by transferring a working copy of the beta-globin gene to blood stem cells using a retrovirus.

In 2012, Glybera became the first viral gene-therapy treatment approved in Europe, which uses an adeno-associated virus to deliver a working copy of the LPL gene to muscle cells to help break down fats in the blood.

Researchers are developing gene therapies for Parkinson's disease by introducing three genes into cells to give them the ability to produce dopamine.

Genome editing technologies, such as Zinc Finger, TAL Effector Nuclease, CRISPR/Cas9, and MegaTals, allow genetic material to be added, removed, or altered at specific locations in the genome.

The meiotic cell division process produces gametes with half the number of chromosomes as diploid cells.

Meiosis I consists of two divisions: Meiosis I division I and Meiosis I division II.

The first meiotic division, Prophase I, is a lengthy process consisting of five stages: Leptotene, Zygotene, Pachytene, Diplotene, and Dictyotene.

During the Leptotene stage, chromosomes appear as long, thin threads that are attached to the nuclear envelope at both ends by specialized structures called attachment plaques.

In the Zygotene stage, homologous chromosomes begin to pair and synapse, forming a synaptonemal complex.

During the Pachytene stage, the chromosomes shorten and thicken, and large recombination nodules are seen on the synaptonemal complex. Exchange of chromatid segments (crossing-over) occurs between non-sister chromatids of the chromosomes.

In the Diplotene stage, the synaptonemal complex disappears, and homologous pairs remain joined only at their chiasmata regions.

Chiasmata, the points where crossing-over occurs, are important for chromosome segregation and morphologically represent the genetic phenomenon of crossing-over.

At the end of Prophase I, the homologous chromosomes are mixed, the nuclear envelope disappears, and the spindle forms. The bivalents (paired homologous chromosomes) are located on the metaphase plate, and independent assortment occurs during anaphase I.

Each gamete receives a unique combination of maternal and paternal chromosomes, ensuring genetic diversity.