How Modern Biotechnology is Shaping Our Future

by Illia Petrov          Biopharma insight

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Covid 19 pandemic that we went through revealed the fragility of our world. Despite the undeniable technological advancements of the past century, the challenges we are facing are still numerous and require immediate action. The midway report on Sustainable Development Goals released by the UN in 2023 showed that out of ca. 140 measurable targets, 50% show moderate or severe deviations from the desired trajectory and more than 30% have experienced no progress or regression below the 2015 baseline.

On the other hand, the biotech sector’s role in healthcare, agriculture, and environmental sustainability is continuously expanding. Therefore, in this article, we would like to present you with nontrivial areas where biotech developments are helping to shape the future.

 

AI-driven protein design

After Deep Mind’s release of AlphaFold, an AI tool capable of predicting protein’s 3D structure based on amino acid sequence, a wave of other AI-driven methods emerged with the aim of achieving a goal even more grand: designing novel proteins with the desired function.

One of such deep learning tools, RF Fusion, was released in 2023. RFdiffusion was designed for generating novel proteins with potential applications in medicine, vaccine development, and advanced materials, developed collaboratively by computational biologists from UW Medicine, Columbia University, and MIT.

RELATED VIDEO: Unlocking Protein Design with AI: Cradle.Bio's Journey

RFdiffusion is based on a guided diffusion model inspired by image-generation tools like DALL-E. The approach involves designing proteins by manipulating amino acid sequences, which are the fundamental building blocks of proteins.

The specific sequence of amino acids dictates the protein's structure and function, impacting diverse biological processes from oxygen transport to enzyme activity. One of the tool’s key capabilities is efficiency and speed, outperforming existing methods in, for example, designing protein monomers with specific topologies, creating protein binders, and developing symmetric oligomers. It has also been effective in scaffolding enzyme-active sites and designing proteins for therapeutic and metal-binding purposes.

RFdiffusion's success includes creating proteins with enhanced binding properties, such as those that bind more effectively to target hormones than previously designed proteins or small molecules, marking the tool’s potential in developing advanced diagnostics and therapies.

 

Helping agriculture adapt to the consequences of climate change

Agricultural biotechnology provides ways to develop plant and animal species that are adapted to changing environmental conditions, such as drought, temperature increases, or new diseases. For instance, cattle exhibit genetic variations that affect their ability to regulate body temperature under heat stress.

Key mutations in the prolactin receptor gene (PRLR), known as frame-shift mutations, result in a short, sleek hair coat, enhancing heat tolerance. These mutations, initially identified in breeds derived from criollo cattle, have been introduced into dairy cattle in Puerto Rico, Florida, and New Zealand to improve heat resistance.

Another significant mutation involves the HSPA1L gene, a heat shock protein 70. This mutation leads to a stronger transcriptional response to heat stress, increasing cellular survival at high temperatures. Identifying and using such genetic variations presents a promising strategy to enhance thermotolerance in cattle.

 

From organ-on-a-chip to patient-on-a-chip: advancing drug development

One of the reasons for the high cost of drug development and safety testing stems from the limitations of current preclinical models. These models often fail to accurately represent how drugs behave in the human body, leading to potential side effects and unexpected outcomes. To address this, scientists are seeking alternatives to traditional cell cultures and animal testing.

One promising approach is the use of organoids, the 3D models formed by self-assembling stem cells into mini-organs. While organoids offer a more realistic representation of human biology, they still cannot fully represent the dynamic nature of real organs and fail to simulate the interactions between different organs in the body.

Here comes organ-on-a-chip technology, also known as organ chips.

These chips are microfluidic devices that aim to replicate the functions of human organs in vitro. Unlike static organoid cultures, organ chips allow for the flow of fluids, mimicking the dynamic exchange of nutrients and signals that occur in living tissues. By integrating multiple mature tissues on a chip and enabling communication through fluid perfusion, scientists hope to create a more comprehensive "body on a chip" model that closely resembles human physiology.

In a study published in Nature Biomedical Engineering, researchers made significant progress towards this goal. They developed a multi-organ chip system that integrated mature heart, liver, bone, and skin tissues, allowing them to interact and communicate as they would in the human body.

READ ALSO: Beyond Animal Testing: Organ-on-a-Chip Companies Usher in a New Era for Drug Trials

The tissues were cultured within their unique microenvironments, separated by an endothelial layer, and connected to a recirculating bloodstream. This setup enabled the tissues to communicate and maintain their phenotypes, providing a more realistic model for studying drug metabolism and toxicity.

While the multi-organ chip system is a remarkable achievement, there are still challenges to overcome. The current system includes only a limited number of tissues, limiting its ability to capture the complexity of the whole human physiology. Future research will focus on developing internal circulation systems to provide fluid flow for the engineered multi-organs. However, this scientific advance brings us closer to the ultimate goal of creating patient-specific models for drug testing and personalized medicine. The potential of these organ chips holds promise for improving drug development and patient care in the future.

 

mRNA vaccines and RNA therapies 

Messenger RNA (mRNA) vaccines against Coronavirus disease from Pfizer and Moderna illustrated how powerful RNA-based treatments can be. RNAs are a class of molecules that modulate cellular processes without incorporation into DNA. They act by directly producing antigens inside our cells and triggering the necessary immune reactions for us to have a cell memory about the virus in the future. This discovery has granted Katalin Karikó and Drew Weissman a Nobel Prize in Physiology and Medicine in 2023. 

The major advantage of mRNA vaccines is the speed at which they can be developed. For attenuated vaccines (measles, mumps, or rubella vaccines) or inactivated vaccines (flu and polio vaccines), actual pathogens must be transported and replicated during the manufacturing process.

So, if a new pathogen were to emerge, an mRNA vaccine would theoretically be a solution to ensure a fast response to this threat. Both clinical trials and real-world studies investigating the capabilities of mRNA COVID-19 vaccines have shown efficacy.

For instance, the likelihood of contracting COVID-19 if you’ve been fully vaccinated with an mRNA vaccine is less than 10 percent. Considering their high efficacy and development speed, mRNA vaccines are now being developed against various infectious diseases, cancer tumors, genetic diseases, and heart failure.

 

Preventing the energy crisis with MFCs

Microbial fuel cells (MFCs) are a transformative technology in biotechnology, efficiently converting organic waste into electrical energy. This process not only generates electricity but also valorizes waste materials, contributing to environmental pollution reduction.

At the core of MFC technology is a microbial consortium, a diverse group of microorganisms that decompose organic waste. This bioconversion process is typically quantified by power density, with some MFCs achieving power densities as high as 4.5 W/m³. This metric is crucial for evaluating the efficiency and potential scalability of MFC systems.

MFCs have been successfully employed with a variety of organic wastes. For instance, certain MFCs using dairy effluent have demonstrated not only electricity generation but also significant pollutant reduction, including up to 88% sulfate, 92% phosphorous, and 100% nitrate removal.

Similarly, experiments with vegetable waste and fruit peels like onions, blueberries, and papayas have shown promising results. This way of converting organic waste into electric energy could be a way to kill two birds with one stone: controlling environmental pollution and producing electric energy in a sustainable way.

Topics: Industry Trends   

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