Programming Biology
The Abudayyeh–Gootenberg lab develops cutting-edge programmable tools for biology by combining natural biological systems, mechanism-inspired design, and machine learning to achieve unprecedented control of genomes, transcriptomes, and cells. Through this innovative approach, we are advancing three major frontiers: developing revolutionary anti-aging interventions by unraveling the mechanisms of cellular aging, creating next-generation programmable medicines for treating genetic diseases and cancer, and applying AI and machine learning to understand biological complexity from proteins to cells.
Unravelling Cellular Aging
Decoding aging in HSCs using biological clocks and gene regulators.
Aging clocks and transcription factor (TF) screening shed light on the molecular mechanisms driving hematopoietic stem cell (HSC) aging and immune decline. Aging clocks measure biological age at the single-cell level, uncovering patterns of premature aging linked to blood disorders. TF screening identifies key regulatory proteins that govern gene expression, distinguishing those that preserve youthful functions from those that accelerate aging. By mapping the interplay between epigenetic and transcriptional changes in HSCs, these tools open new avenues for therapies to rejuvenate aged HSCs, boost immune health, and treat age-related blood disorders.
Hair Rejuvenation: The Power of Secreted Factors
Exploring secreted factors for hair rejuvenation focuses on the proteins, peptides, and bioactive molecules released by cells that can stimulate hair growth and improve follicle health. These secreted factors can activate signaling pathways in hair follicle stem cells, promote angiogenesis for better nutrient supply, and modulate inflammation, all of which are crucial for hair regeneration. This research has the potential to find new topical treatments derived from the secretome to harness the body’s natural healing mechanisms.
Next-Generation Therapeutics
Secretome Screening: Unlocking New Peptide Interventions for Disease.
Screening peptide factors unlocks new disease interventions by identifying powerful peptides and secreted factors that can target specific pathways. This innovative approach allows for high-throughput testing to discover potential drug candidates, paving the way for personalized medicine and finding new anti-aging interventions. By harnessing the unique properties of peptides, we can revolutionize treatment strategies and improve patient outcomes.
Transforming genetic therapy: harnessing RNA editing with trans-splicing and Cas7-11 for precise, personalized medicine.
RNA editing through trans-splicing and Cas7-11, a CRISPR-Cas member, enables precise genetic manipulation with therapeutic potential. Trans-splicing joins exons from different RNA molecules, correcting mutations by replacing defective sequences. Cas7-11 directly edits RNA transcripts and allows multiplexing to target multiple RNA molecules simultaneously. These techniques enable precise RNA-level corrections, improved gene expression regulation, and personalized treatments for genetic disorders and cancers.
Revolutionizing mRNA delivery: leveraging protein corona methods to retarget lipid nanoparticles for enhanced specificity and efficacy.
Protein corona methods enhance mRNA delivery by modifying the proteins that bind to lipid nanoparticles (LNPs), affecting their distribution and cellular uptake. By designing LNPs to interact with specific proteins or adding targeting ligands, researchers can improve delivery specificity and efficiency to target cells. This reduces off-target effects and enhances therapeutic efficacy, advancing mRNA vaccines, gene therapies, and other biopharmaceuticals.
RADARS: Targeting Cancer and Immunity at the Cellular Level.
RNA sensing for targeting specific cell states in cancer and immunity is an innovative approach that leverages the unique characteristics of RNA molecules to identify and manipulate distinct cellular behaviors. By detecting various types of RNA, such as mRNA, microRNA, and long non-coding RNAs, using our sensing tool RADARS, researchers can gain insights into the underlying biology of cancer and immune cells. These RNA profiles serve as biomarkers that reflect specific cellular states, helping to differentiate between aggressive tumor subpopulations and more benign ones, as well as activated versus resting immune cells.
Decoding Biological Complexity
Accelerating drug discovery with Virtual Cells: simulating life to unlock new treatments
Building a "Virtual Cell" could revolutionize drug development by digitally simulating a living cell’s complex inner workings, from protein interactions to genetic responses. This digital model would allow researchers to quickly test drug effects, predict side effects, and simulate disease conditions—cutting down the time, cost, and risk associated with traditional lab trials. By incorporating data from large-scale omics data, both publicly and from our lab, the Virtual Cell will give researchers a powerful tool to identify new biology and refine drug candidates early, aiming for tailored therapies with higher success rates. It’s a bold leap toward revolutionizing biological and drug discovery.
Using LLMs to revolutionize directed evolution and protein engineering.
Large language models are revolutionizing directed evolution and protein engineering. These cutting-edge AI tools predict how amino acid changes influence protein functions, significantly speeding up the design of novel proteins and enzymes. This innovative approach not only enhances efficiency but also paves the way for exciting breakthroughs in biotechnology’s next generation.