Current Methods for the Development and Assessment of Nucleic Acid-Based Regenerative Immunotherapies

TOPICAL COLLECTIONS

Guest Editor

Dr. Theresa Raimondo

Brown University

Theresa Raimondo is an assistant professor of engineering at Brown University and a member of the Legorreta Cancer Center and the Brown RNA Center. Dr. Raimondo’s research focuses on the design of targeted drug-delivery vectors and novel RNA therapeutics for immunoengineering, cancer, and tissue regeneration. Her research primarily concentrates on developing novel lipid nanoparticles (LNPs) for RNA-based therapies and ex vivo systems to model healthy, metastatic, or injured tissues. By using engineering approaches to optimize both LNP formulation and RNA design (sequence and chemical modifications), Dr. Raimondo seeks to better understand how RNA-LNPs modulate immunity and to use this understanding to develop new regenerative therapies. She has four patents surrounding targeted RNA-LNPs, adjuvanted vaccines, and siRNA immunotherapy. Her work on immune-modulating gold nanoparticle-protein conjugates was among the first to demonstrate that sustained, biomaterial-driven macrophage polarization results in the regeneration of functional muscle fibers. Dr. Raimondo received postdoctoral training with Dr. Anderson and Dr. Langer at MIT and PhD with Dr. Mooney at Harvard University. Dr. Raimondo has received several awards, including the NEBEC Faculty Innovator Award, MIT Faculty Founder competition finalist, and the American Cancer Society-Institutional Research Grant.

Collection Overview

zAcute inflammation is a protective response that kills invading pathogens, is self-limiting, and promotes functional tissue regeneration. Uncontrolled immune activation, however, leads to chronic inflammation, tissue damage, and disease progression. Increasing evidence suggests that dysregulated immunity is pathogenic in many prevalent diseases, including cardiovascular, metabolic, and neurodegenerative, as well as genetic diseases, including muscular dystrophies. The biological complexity of chronic inflammation, with multiple cell types and cytokines playing divergent context-dependent roles, makes developing anti-inflammatory therapeutics that promote functional tissue regeneration difficult.

Nucleic acid-based therapeutics are rapidly advancing as a potential strategy to generate therapeutic immune responses, target drug delivery, and directly promote tissue regeneration. There is an increasingly symbiotic relationship between biomaterials and nucleic acid-based therapeutics. Biomaterials and nanoscale delivery vectors play a central role in protecting DNA and RNA from degradation in vivo, spatiotemporally targeting delivery, aiding intracellular uptake, and modulating immunogenicity. Nucleic acids can contribute intricate structural complexity to biomaterials and facilitate nuanced conjugation with targeting moieties. Additionally, engineered RNA (such as circular RNA, guide RNA, or peg RNA) and the incorporation of chemical modifications (notably pseudouridine in mRNA-based SARS-CoV-2 vaccines) can be employed to optimize nucleic acid-based immunotherapies.

This collection compiles methods surrounding the design, optimization, and assessment of nucleic acid-based regenerative technologies. These include, but are not limited to:

• polymeric, lipid, and inorganic nanomaterials

• hydrogel, polymer, and scaffold-based materials for nucleic acids

• nucleic acid-based targeted delivery

• barcoding, machine learning, and spatial transcriptomics for therapeutic optimization

• the fabrication of novel nucleic acid constructs