Recombinant human proteins used to treat disease

· Recombinant human proteins = human proteins made by genetically engineered organisms or cells using recombinant DNA.
· Main advantage: protein has the same amino acid sequence as the human protein, so it is usually more effective and less likely to cause immune rejection than animal-derived proteins.
· Production can be large-scale, reliable, consistent, and does not depend on extracting proteins from animals or donated human tissue.
· Recombinant products reduce risks linked with older sources, such as contamination with pathogens from donated blood or tissues.
· Insulin: used to treat diabetes mellitus when the body cannot produce enough insulin or cannot use it effectively.
· Recombinant insulin avoids problems with pig/cow insulin, such as allergic reactions, religious/ethical concerns, and limited animal supply.
· Factor VIII: used to treat haemophilia A, where blood clotting is impaired due to lack of functional factor VIII.
· Recombinant factor VIII avoids dependence on donated blood plasma and reduces risk of blood-borne infection.
· Adenosine deaminase (ADA): used for ADA deficiency, a cause of severe combined immunodeficiency (SCID).
· ADA treatment can improve immune function because ADA is needed for normal lymphocyte function.

Recombinant human insulin can be produced by inserting a modified human insulin gene into a bacterial plasmid. The transformed bacteria express the gene and produce insulin, which is then purified for medical use. Source

Advantages of recombinant proteins: exam phrasing

· Human protein sequence → more compatible with patients.
· Lower immune response than non-human animal proteins.
· No need to extract from animals → fewer ethical/religious objections.
· No need for donor blood/tissue → lower risk of pathogen transmission.
· Mass production → reliable supply and standardised dose/purity.
· Specific examples to memorise: insulin, factor VIII, adenosine deaminase.

Factor VIII is a blood-clotting protein needed for normal clot formation. Recombinant factor VIII can replace the missing or faulty protein in people with haemophilia A. Source

Genetic screening

· Genetic screening = testing DNA to identify alleles, mutations, or genetic markers linked with inherited disease or increased disease risk.
· It can be used before symptoms appear, so people can make informed medical and lifestyle decisions.
· Screening can identify carriers, affected individuals, or people with increased risk of developing a condition.
· Results can guide monitoring, early treatment, preventive action, and family planning.
· Screening is especially useful when there is a family history of a genetic condition.
· Results should usually be explained with genetic counselling, because risk is often probabilistic, not certain.

Examples of genetic screening

· Breast cancer: BRCA1 and BRCA2
· BRCA1 and BRCA2 are genes involved in DNA repair and tumour suppression.
· Mutations in these genes increase risk of breast cancer and ovarian cancer.
· Screening can allow increased surveillance, preventive surgery, or earlier treatment decisions.
· Important exam phrase: a positive result means increased risk, not certainty of cancer.

· Huntington’s disease
· Caused by a dominant allele involving abnormal repeats in the HTT gene.
· Genetic screening can identify whether a person has inherited the allele before symptoms appear.
· Advantage: allows planning for future care, family decisions, and psychological preparation.
· Limitation: there may be no cure, so testing can cause anxiety or distress.

· Cystic fibrosis
· Caused by mutations in the CFTR gene; usually inherited as an autosomal recessive condition.
· Genetic screening can identify carriers, affected embryos/foetuses, or affected newborns.
· Advantage: helps reproductive decisions and enables earlier treatment/support.
· Limitation: many possible CFTR mutations exist, so screening may not detect every mutation.

BRCA1 and BRCA2 screening identifies inherited mutations that increase cancer risk. The diagram is useful for showing that screening predicts risk, not certainty. Source

Huntington’s disease is inherited as an autosomal dominant condition. A pedigree helps show that an affected heterozygous parent has a 50% chance of passing the allele to each child. Source

Gene therapy

· Gene therapy = treating a genetic disease by introducing a functional allele/gene into a patient’s cells.
· The aim is for cells to produce a functional protein that is missing, faulty, or present in too small an amount.
· The functional gene is usually delivered using a vector, often a modified virus.
· Gene therapy may be somatic: body cells are altered, so the change is not inherited.
· Germline gene therapy would alter gametes/embryos and could be inherited, but it raises major ethical issues and is not expected as routine treatment.
· Success depends on delivering the gene to enough target cells and achieving long-term gene expression.

Gene therapy uses a vector to deliver a functional gene into target cells. If the gene is expressed, the cell can make a functional protein that helps treat the genetic disease. Source

Gene therapy examples

· SCID: severe combined immunodeficiency
· SCID causes a severely weakened immune system, often due to defective genes affecting lymphocyte development/function.
· In ADA-SCID, patients lack functional adenosine deaminase, so lymphocytes do not function normally.
· Gene therapy can add a functional ADA gene into the patient’s cells so ADA is produced.
· Benefit: can restore immune function and reduce dependence on repeated enzyme replacement or isolation from pathogens.

· Inherited eye diseases
· Some inherited eye diseases are caused by a mutation in a single gene needed for normal retinal function.
· Gene therapy can deliver a functional copy of the gene to cells in the retina.
· The eye is a useful target because it is small, accessible, and immune responses may be more limited than in some tissues.
· Benefit: may slow disease progression or improve vision if enough retinal cells are still alive.

Social and ethical considerations

· Informed consent: patients must understand risks, benefits, uncertainty, and possible consequences.
· Privacy and confidentiality: genetic data is sensitive and could affect family members as well as the patient.
· Discrimination risk: employers or insurers could misuse genetic screening results.
· Psychological impact: knowing future disease risk may cause anxiety, especially for untreatable diseases such as Huntington’s.
· Family implications: one person’s result may reveal risk for relatives who may or may not want to know.
· Embryo/foetal screening: raises ethical issues about selection, termination, disability, and parental choice.
· Access and cost: expensive screening or gene therapy may increase healthcare inequality.
· Safety: gene therapy may trigger immune responses, insertional mutation, or unintended effects.
· Somatic vs germline: somatic therapy affects only the patient; germline changes would affect future generations and are more ethically controversial.
· Balanced exam answer: discuss both medical benefits and ethical/social risks, then give a reasoned judgement.