Is GENE THERAPY implanting new genes or demethylating existing genes?

 

Gene therapy encompasses a range of techniques, and its objective is to treat or prevent diseases by manipulating genes.

Two primary approaches in gene therapy are:

1. Introducing or Replacing Genes: This involves delivering a new or functional copy of a gene into cells where a non-functional or faulty gene is causing disease. Common methods include using viral vectors, which have been engineered to carry therapeutic genes instead of their viral genes, to deliver the desired gene into target cells.

2. Gene Editing: Instead of adding a functional copy of a gene, researchers can also directly edit a faulty gene within the body. Tools like CRISPR/Cas9 have made it possible to target specific DNA sequences, allowing for precise alterations of the genetic code.

Now, concerning demethylation:

Methylation is a type of epigenetic modification where a methyl group is added to a cytosine base in DNA. When genes are hypermethylated (especially at promoter regions), their expression is often repressed. Demethylation, the removal of the methyl group, can reactivate the expression of genes.

Although demethylation isn't "gene therapy" in the classical sense of replacing or correcting faulty genes, modifying epigenetic markers like methylation can be considered a form of gene regulation therapy. By changing methylation patterns, one can influence gene expression and potentially treat certain conditions.

So, gene therapy can involve implanting new genes, editing existing genes, or regulating the expression of genes through epigenetic modifications like demethylation. The choice of approach depends on the specific condition being addressed and the mechanism by which the disease operates.

Can medication manipulate GENES?

 

Yes, some medications can influence gene expression or the function of genes. Here are a few ways in which this happens:

1. Epigenetic Modifiers: Some drugs can modify the epigenetic landscape of the genome. For instance, there are drugs that inhibit DNA methyltransferases, which are enzymes responsible for adding methyl groups to DNA. By inhibiting these enzymes, these drugs can lead to the demethylation of DNA and potentially reactivate the expression of certain genes. Such drugs can be used in certain cancers, like myelodysplastic syndromes, where abnormal DNA methylation patterns play a role in the disease process.

2. RNA Interference (RNAi): Some drugs are designed to harness the natural RNA interference pathway, which involves small RNA molecules inhibiting gene expression. These drugs can specifically target and degrade messenger RNA (mRNA) corresponding to a particular gene, thereby reducing its expression.

3. Antisense Oligonucleotides: These are short, synthetic pieces of DNA or RNA that can bind to specific mRNA molecules. By binding to their target mRNAs, they can prevent the mRNAs from being translated into proteins. This approach can be used to reduce the expression of harmful proteins.

4. CRISPR-based Therapies: Although still in early stages of development, some therapeutic approaches aim to use the CRISPR/Cas system, a powerful gene-editing tool, to make precise changes to the DNA in living organisms. These changes might involve fixing a mutation in a gene, deleting a harmful gene, or adding a therapeutic gene.

5. Regulation of Transcription Factors: Some drugs act by modulating the activity of transcription factors, which are proteins that help turn genes on or off. By influencing these transcription factors, the drugs can upregulate or downregulate the expression of target genes.

6. Hormones and Receptors: Some medications, like steroids or thyroid hormone, act by binding to specific receptors in the cell. These receptor-hormone complexes can then migrate to the cell nucleus and influence the expression of specific genes.

It's important to note that while many drugs influence gene expression, not all of them directly modify the DNA sequence. Most act by influencing the machinery that reads out the genetic code or the epigenetic markers that regulate gene activity. The choice to use a particular drug or approach depends on the specific condition being addressed and the underlying genetic or molecular basis of that condition.

Name drugs that manipulate GENES

Several drugs and therapies have been developed or are in development that can influence gene expression, function, or the underlying DNA itself. Here are some examples:

1. Epigenetic Modifiers:

   • DNA Methyltransferase Inhibitors (DNMTi): Drugs like azacitidine (Vidaza) (for chronic myelomonocytic leukaemia (CMML) and decitabine (Dacogen) are used to treat myelodysplastic syndromes (MDS) and certain types of leukemia. They work by inhibiting DNA methyltransferases, leading to DNA demethylation and reactivation of certain genes.
   • Histone Deacetylase Inhibitors (HDACi): Examples include vorinostat (Zolinza) and romidepsin (Istodax). These drugs influence gene expression by affecting histone acetylation, another form of epigenetic modification.

2. RNA Interference (RNAi) Therapies:

   • Patisiran (Onpattro): This is an RNAi therapeutic approved for the treatment of the hereditary transthyretin-mediated amyloidosis (hATTR). It targets and degrades the mRNA for transthyretin (TTR) protein.

3. Antisense Oligonucleotides:

   • Nusinersen (Spinraza): Used to treat spinal muscular atrophy (SMA), it modulates the splicing of the SMN2 gene to increase the production of the functional SMN protein.
   • Eteplirsen (Exondys 51) and Golodirsen (Vyondys 53): These are used to treat certain forms of Duchenne muscular dystrophy (DMD). They lead to exon skipping during mRNA splicing, producing a partially functional dystrophin protein.

4. Gene Therapies:

   • Voretigene neparvovec-rzyl (Luxturna): This is a gene therapy for a specific type of inherited retinal dystrophy caused by mutations in the RPE65 gene. It introduces a correct copy of the RPE65 gene into retinal cells.
   • Zolgensma (onasemnogene abeparvovec-xioi): This is a gene therapy for spinal muscular atrophy (SMA), introducing a functional copy of the SMN1 gene to replace the faulty one.

5. CRISPR-based Therapies:

   • While no CRISPR-based therapies were approved as of my last training data in January 2022, multiple clinical trials were underway. These trials are exploring the potential of CRISPR to correct genetic mutations in diseases like sickle cell anemia and beta-thalassemia.

6. Hormones and Receptors:

   • Drugs like tamoxifen and raloxifene are selective estrogen receptor modulators (SERMs). By binding to estrogen receptors, they can influence the expression of genes that are regulated by estrogen.

It's essential to understand that these therapies, especially gene therapies and CRISPR-based interventions, are complex and come with their own set of risks and challenges. They are typically pursued for conditions where the potential benefits outweigh the risks, especially for severe genetic disorders.