Emerging Biotechnology Set to Revolutionise Medicine

Introduction

Biotechnology is driving a profound shift in medicine towards more personalised treatments. Innovations like CRISPR-based gene editing and 3D bioprinting are revolutionising how we approach disease treatment and organ transplantation. These advancements not only promise targeted therapies but also hold the potential to address global challenges such as organ shortages and genetic disorders.

3D Bioprinting in Space

Bioprinting, or biological printing, uses living cells, proteins, and nutrients as raw materials and, according to field experts, holds the potential to produce human tissues for treating injuries and diseases, as well as creating entire organs for transplants. What might be even more surprising is that such research is currently being conducted in space, where microgravity offers several advantages, such as improved cell growth and stability, more accurate modelling of human tissue, and reduced sedimentation. In the near-weightlessness of a space station's orbit, cells can grow more naturally in three dimensions, and materials do not settle or deform under their weight as they do on Earth. An American space infrastructure leader, Redwire Corporation, developed the BioFabrication Facility (BFF), where in 2023 a human knee meniscus, i.e., a c-shaped piece of tissue that acts as a shock absorber when walking, running, etc., was successfully printed and currently cardiac tissue samples are being printed and processed to eventually create replacement hearts for patients with cardiovascular disease.

With funding from NASA, LambdaVision Inc. partnered with Space Tango Inc. to develop the first protein-based artificial retina capable of restoring eyesight. This initiative was launched following the discovery that gravity negatively impacts the manufacturing process, where alternating layers of a light-activated protein and a binder are applied to a film. Researchers hypothesised that producing these films in microgravity could result in more stable films with higher optical clarity. Since then, LambdaVision has successfully manufactured multiple 200-layer artificial retina films aboard the International Space Station (ISS) and is working to commercialise its technology.

A joint effort by the European and German space agencies has led to the development of a prototype portable handheld bioprinter designed to accelerate the healing process in space, where wounds tend to heal more slowly. This device creates a patch from the patient's skin cells, significantly reducing the risk of rejection by the immune system. The bioprinter has been successfully tested in microgravity, and researchers are now comparing space-printed patches with those printed on the ground before making this technology available to healthcare professionals on Earth.

CRISPR-Based Gene Editing

CRISPR, short for Clustered Regularly Interspaced Short Palindromic Repeats, is a powerful tool that scientists use to edit genes. Think of it as a pair of molecular scissors that can cut DNA at specific locations. The Cas9 protein is the 'scissors' in this system and is the most widely used for gene editing. This technology has shown great promise for gene therapy, cancer treatment, infectious disease control, and immune system modulation.

The process of gene editing starts with a guide RNA (gRNA), which is designed to find a specific sequence in the DNA. You can think of the guide RNA as a GPS that directs the system to the exact location in the DNA where an edit needs to be made. Once the gRNA finds its target, it brings along a protein called Cas9, which cuts the DNA at the precise spot identified by the gRNA. This cutting action allows scientists to turn off a gene or replace a faulty gene with a correct version. After the cut, the cell naturally tries to repair the break. Sometimes the cell does this quickly and imperfectly, thereby disabling the gene at that spot. Other times, if scientists provide a template with the correct DNA sequence, the cell can use this to repair the break.

CRISPR is particularly suitable for monogenic diseases, which are caused by mutations in a single gene. Conditions like sickle cell anaemia, cystic fibrosis, and Huntington's disease are prime targets because the precise nature of the genetic defect allows CRISPR to correct the mutation at the DNA level. In sickle cell anaemia, CRISPR can modify the gene responsible for producing abnormal haemoglobin, potentially curing the disease by restoring normal haemoglobin production.

Cancer Treatment Applications

In cancer treatment, CRISPR is being used to modify genes involved in tumour progression and resistance to therapy. One approach involves knocking out genes that enable cancer cells to evade the immune system or become resistant to drugs. For example, targeting mutations in the BRCA1 or BRCA2 genes, which are known to increase the risk of breast cancer, can prevent cancer cells from effectively repairing their DNA. This makes them more susceptible to treatments like PARP inhibitors, which further disrupt DNA repair, leading to increased cancer cell death and reducing the likelihood of drug resistance. Additionally, CRISPR is used to engineer T cells, a type of immune cell, to better recognise and attack cancer cells. In CAR-T therapy, a patient's T cells are extracted, and genetically modified using CRISPR to add new receptors, which are designed to recognise and bind to proteins (antigens) found on cancer cells, and then these T cells are reinfused into the patient to target and destroy cancer cells more effectively.

Liquid biopsies play a crucial role in this process by providing a non-invasive way to detect and measure biomarkers – biological molecules, such as circulating tumour DNA, that indicate the presence or progression of cancer. These biomarkers reveal the genetic mutations present in the tumour, enabling doctors to tailor CRISPR-based treatments to the specific genetic profile of the cancer. This targeted approach increases the precision of the treatment and reduces the risk of affecting healthy cells. As our understanding of genetics deepens, CRISPR could enable the development of therapies tailored to an individual's entire genetic profile, leading to even more personalised treatments with fewer side effects.

Infectious Diseases and Vision Restoration

CRISPR has potential applications in treating infectious diseases by targeting and editing viral genomes within infected cells. For example, in the case of HIV, CRISPR can be used to remove the integrated viral DNA from the host genome, thereby preventing the virus from replicating. This approach could lead to a functional cure for chronic viral infections by permanently disrupting the viral genome within the host cells.

Inherited eye diseases, such as Leber congenital amaurosis, which result from specific genetic mutations, are also being targeted by CRISPR-based therapies. Researchers can correct the mutation responsible for the disease by delivering CRISPR components directly to the retina. Early clinical trials have shown potential in restoring partial vision by repairing the defective gene in the retinal cells, offering a promising approach for genetic forms of blindness.

Xenotransplantation Advancements

CRISPR-Cas9 technology has recently been used to make animal organs more compatible with the human body. In March 2024, surgeons at Massachusetts General Hospital successfully transplanted a pig kidney into a living human recipient. To improve compatibility, 69 genetic modifications were made, removing harmful pig genes and adding human genes. Additionally, scientists deactivated viruses typically found in pigs to reduce the risk of infection. This successful procedure marks a significant advance in xenotransplantation—the transplantation of organs or tissues between species—and offers hope for addressing the global organ shortage.

Emerging CRISPR Technologies

While Cas9 has been widely successful, it can only edit DNA at sites where a specific short DNA sequence, called a PAM sequence, is present, which limits the enzyme's ability to target certain areas of the genome. Nevertheless, new techniques have been discovered. Base editing allows for the direct conversion of one DNA base into another without cutting the DNA strand. This method is particularly useful for correcting single-point mutations, reducing the risk of unintended errors that can occur with traditional CRISPR-Cas9. Prime editing offers even more flexibility by enabling precise insertions, deletions, or replacements of DNA sequences. It uses a guide RNA and a reverse transcriptase enzyme to make these edits without relying on the cell's repair mechanisms. This approach minimises off-target effects and expands the range of genetic mutations that can be corrected, making it a powerful tool for future gene therapies. Currently, Cas9 remains the most used gene editing method due to its simplicity and cost-effectiveness, but this is likely to change.

CRISPR, despite its powerful gene-editing capabilities, faces several limitations. One major concern is off-target effects, where the system may inadvertently cut DNA at unintended sites, potentially causing unwanted mutations. Additionally, effectively delivering CRISPR components into the correct cells within the body remains a significant challenge. Ensuring that the CRISPR machinery reaches and operates in the right cells without triggering immune responses or affecting other tissues is crucial for its safe and effective use in therapies. These issues highlight the need for further refinement and development of CRISPR technology.

Future Outlook

CRISPR and 3D bioprinting are just the beginning of a wave of biotechnological breakthroughs reshaping the future of healthcare. From lab-grown organs that could eliminate the need for donors, to brain-computer interfaces that may one day restore movement or memory, the possibilities seem endless. Advancements in microbiome manipulation, cellular anti-ageing therapies, and quantum-powered drug discovery could further transform the way we treat, prevent, and even reverse disease. Medicine is guaranteed to remain a critical focus of research as humans continue to seek improved quality of life. Unlike many sectors that are undergoing layoffs due to AI, the healthcare field is projected to grow steadily with a constant need for skilled professionals.

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