Principles of Gene Therapy Applicability

Terms of Applicability

Type of Inheritance

Mendelian diseases, determined by the action of a single gene, are better candidates than multifactorial diseases, which rely on the joint action of several genes and are influenced by environmental factors.

Pattern of Inheritance

Recessive diseases are better candidates for gene therapy treatment than dominant ones.

Nature of the Mutation

• Recessive Mutations: When the affected gene produces an inadequate protein, the introduction of a normal copy of the gene is sufficient to produce a functional protein and correct the condition.
• Dominant Mutations: Replacing one gene is insufficient because the mutant gene continues to be read and translated. These require more complex strategies, such as blocking the specific mutated gene or directing the correction of the mutation.

Control of Gene Expression

Genes that do not require strict control of their expression are the easiest to treat. Conversely, when expression must be tightly regulated, significant challenges arise.

For example, in β-thalassemia, the inserted β-globin gene requires precise production levels equal to α-globin. This necessity for strict control has hindered progress in applying gene therapy to this blood disease.

Size of DNA to be Inserted

Genes with small coding sequences are ideal candidates. Genes with large coding DNA are difficult to transfer into cells due to the challenge of finding suitable vectors.

Tissue Type

Diseases are more treatable if they are expressed in tissues where cells can be easily extracted, grown in vitro, modified, and reintroduced into the body. Ideally, these cells should be long-lived to persist throughout the patient's life. The best candidates for these procedures are primarily bone marrow, skin, and liver tissues.