Nawaz Lab (Gothenburg University)

Understanding disease through extracellular vesicles (EVs), and developing EV-based therapeutics
Reprogramming EVs as precision delivery systems for nucleotide therapeutics (siRNA, antisense oligonucleotides, mRNA and CRISPR) to specific cells and tissues

By applying cutting edge technologies, we (i) determine how EVs induce and modulate disease states, and act as disease fingerprints and (ii) we reprogram/engineer EVs to deliver nucleotide–based therapeutics into tissues related to metabolic diseases and comorbid conditions such as adipose, liver, pancreas, and heart. Within this framework, our research is organized into following interconnected themes:

1. Understanding disease through EVs: EVs are lipid bilayer nano- and micro-sized vesicles which are continuously released from tissues under both healthy and pathological conditions. EVs mirror the functional status of their tissues of origin, inform systemic or paracrine complications, and possess the capability to reprogram the functional states of recipient tissues by transferring bioactive molecules. We investigate how organs communicate (especially adipose, liver, pancreas, heart, brain) through EVs under metabolic conditions (obesity, diabetes, and liver-originated diseases), cancers and neurodegenerative diseases. Through this work, we elucidate the changes occurring inside the body, defining entirely new ways of disease onset, progression, and response to therapy reflected through EVs. By uncovering how diseases reshape inter-organ communication via EVs and how EVs, in turn, shape disease biology and response to therapy, we aim to develop entirely new ways of treating diseases.

Extracellular vesicles, including exosomes, transport RNA, proteins, and lipids between cells, reprogramming the functional state of recipient cells and tissues.

2. Developing EV-based precision therapeutics

Using Nano(-EV)technology, we utilize EVs as tools for new therapies to treat diseases.

2.1. Reprogramming EVs as precision delivery systems for nucleotide therapeutics: Leveraging their natural ability to encapsulate and transport biologically active molecules between cells, and organ tropism, we reprogram EVs and engineer them as nano-carriers of nucleic nucleotide-based drugs such as siRNA, antisense oligonucleotides (ASOs), mRNA, and CRISPR components. Via these reprogrammed and engineered EVs, we deliver treatments to specific cells and tissues where disease-causing targets reside, focusing on conditions such as obesity, diabetes, liver-originated diseases, cancers, and neurodegenerative disorders.

2.2. EVs as regenerative nano compounds: EVs obtained from regenerative cell sources, particularly stem cells, naturally carry regenerative and immunomodulatory molecules such as proteins, RNAs, and growth factors with repair-promoting properties. We characterize their bioactivity, potency and develop them as cell-free therapeutic agents to promote tissue repair and restore organ function. We further reprogram these regenerative EVs with chemically modified therapeutic RNAs for inducing tissue healing especially those involved for metabolic comorbid conditions.

3. EVs as disease fingerprints (biomarkers) at nanoscale: Under healthy and pathological conditions, tissues continuously release EVs carrying pathophysiological information including RNAs, proteins, lipids, and metabolites. The molecular cargo of these EVs mirrors the pathological status of the tissues that secrete them, providing dynamic “fingerprints” indicative of disease processes and stage as well as systemic complications. We isolate and characterize EVs from patient-derived clinical samples, and mine disease-associated EV content to develop minimally invasive biomarkers and liquid biopsies of metabolic conditions (obesity, diabetes, cardiovascular disease), neurodegenerative diseases, and cancers.