About

Samagya Banskota, PhD, is an Assistant Professor in Biomedical Engineering at Boston University College of Engineering. She holds a PhD in Biomedical Engineering from Duke University and completed a postdoctoral fellowship in Chemistry and Chemical Biology at the Broad Institute of Harvard and MIT. Her research interests encompass drug delivery, biomolecular engineering, biomaterials design, genome editing, synthetic biology, functional genomics, and protein engineering. Her lab focuses on developing precision genome editing technologies aimed at treating genetic diseases by making targeted DNA modifications. A key aspect of her work involves addressing delivery challenges for therapeutics through the design of genetically-encoded and stimuli-responsive delivery systems, integrating synthetic biology and protein engineering. Additionally, her research explores the biological functions of transposable elements within the human genome, developing genome and epigenome editing technologies to serve as molecular recorders for studying their roles in diseases. Recognized as a Hartwell Investigator, she has been honored as one of MIT Technology Review's 35 Innovators Under 35 and received the Pratt-Gardner Graduate Fellowship.

Research topics

• Biology
• Biophysics
• Chemistry
• Materials science
• Internal medicine
• Nanotechnology
• Pharmacology
• Medicine
• Computational biology
• Combinatorial chemistry
• Genetics
• Cell biology
• Biochemistry

Selected publications

• In vivo base editing rescues liver pathophysiology and peroxisome dysfunction in a mouse model of Zellweger spectrum disorder

  Nature Biomedical Engineering · 2026-04-14

  articleOpen access

  Zellweger spectrum disorder (ZSD) is caused by biallelic loss-of-function variants in PEX genes required for peroxisome biogenesis, which is critical for normal cellular metabolism and signalling. The PEX1-p.G843D (c.2528G>A) allele, present in approximately 30% of individuals with ZSD, frequently results in chronic liver disease that can progress to cirrhosis, hepatocellular carcinoma and degraded neurological health. Here we report the development and application of an adenine base editing strategy to correct an established homozygous Pex1-p.G844D ZSD mouse model that manifests liver pathologies and metabolic dysfunction found in patients. Through intravenous delivery of AAV9 encoding ABE8e-V106W into both neonatal and 4-week-old mice, we achieved up to 60% pathogenic allele correction in the bulk liver. By restoring peroxisome function, base editing eliminated bulk accumulation of very long-chain and branched-chain fatty acids, and toxic C27-bile acid intermediates. Increased levels of phytanic acid, a branched-chain fatty acid that becomes harmful when accumulated, were normalized in blood, liver and brain tissue. Treatment of homozygous Pex1-p.G844D mice resulted in the progressive, dose-dependent normalization of liver transcriptomes and histopathology, accompanied by gains in body weight. Non-viral lipid nanoparticle delivery of ABE8e-V106W mRNA to 4-week-old mice also yielded correction of the Pex1-p.G844D allele in 27% of bulk liver cells. In patient-derived fibroblasts, base editing corrected >80% of PEX1-p.G843D alleles and restored peroxisome homeostasis. Genome-wide experimental and computational off-target analyses found minimal off-target editing in the mouse or human genome. Collectively, these findings suggest that liver base editing over a range of ages may benefit individuals with ZSD and provides a foundation for developing precision gene correction treatments that address the root cause of a wide range of peroxisomal disorders.

  PublisherOA PDFDOI

• Delivery of genome editors with engineered virus-like particles

  Methods in enzymology on CD-ROM/Methods in enzymology · 2025-01-01 · 4 citations

  reviewSenior authorCorresponding
  PublisherDOI

• Preclinical Development of a Genetically Engineered Albumin‐Binding Nanoparticle of Paclitaxel

  Small Science · 2024-09-25 · 8 citations

  articleOpen access

  Nab-paclitaxel (Abraxane), an albumin-bound solvent-free paclitaxel (PTX) formulation that takes advantage of the endogenous albumin transport pathway, is the current gold standard for treatment of solid tumors with PTX. However, nab-paclitaxel has several limitations, including complex manufacturing, immunogenicity, slow drug-release, and a narrow therapeutic window. Nevertheless, no other PTX formulation has gained the Food and Drug Administration approval since Abraxane's 18-year reign. Addressing these concerns, herein, a PTX-loaded nanoparticle of a recombinant polypeptide that-like nab-paclitaxel-capitalizes on the long in vivo half-life of albumin is reported. This genetically engineered nanoparticle packages PTX in the core of the nanoparticle and displays an albumin-binding domain on the exterior of the nanoparticle. Upon in vivo administration, the drug-loaded nanoparticle binds albumin with nanomolar affinity, and acquires an albumin-corona, which eliminates the need to use exogenous albumin. The nanoparticles can be stored at subzero temperature as lyophilized powder without any cryoprotectants for upto a year and can be reconstituted on-demand in aqueous buffer at high concentration, thus greatly simplifying formulation processes. These albumin-binding nanoparticles improve the therapeutic window by at least twofold compared to nonalbumin-binding counterpart and outperform nab-paclitaxel in multiple murine tumor models, results that have been independently replicated by a contract research organization.

  PublisherOA PDFDOI

• Engineered virus-like particles for transient delivery of prime editor ribonucleoprotein complexes in vivo

  Nature Biotechnology · 2024-01-08 · 228 citations

  articleOpen access

  Prime editing enables precise installation of genomic substitutions, insertions and deletions in living systems. Efficient in vitro and in vivo delivery of prime editing components, however, remains a challenge. Here we report prime editor engineered virus-like particles (PE-eVLPs) that deliver prime editor proteins, prime editing guide RNAs and nicking single guide RNAs as transient ribonucleoprotein complexes. We systematically engineered v3 and v3b PE-eVLPs with 65- to 170-fold higher editing efficiency in human cells compared to a PE-eVLP construct based on our previously reported base editor eVLP architecture. In two mouse models of genetic blindness, single injections of v3 PE-eVLPs resulted in therapeutically relevant levels of prime editing in the retina, protein expression restoration and partial visual function rescue. Optimized PE-eVLPs support transient in vivo delivery of prime editor ribonucleoproteins, enhancing the potential safety of prime editing by reducing off-target editing and obviating the possibility of oncogenic transgene integration.

  PublisherOA PDFDOI

• Efficient prime editing in mouse brain, liver and heart with dual AAVs

  Nature Biotechnology · 2023-05-04 · 206 citations

  articleOpen access

  Realizing the promise of prime editing for the study and treatment of genetic disorders requires efficient methods for delivering prime editors (PEs) in vivo. Here we describe the identification of bottlenecks limiting adeno-associated virus (AAV)-mediated prime editing in vivo and the development of AAV-PE vectors with increased PE expression, prime editing guide RNA stability and modulation of DNA repair. The resulting dual-AAV systems, v1em and v3em PE-AAV, enable therapeutically relevant prime editing in mouse brain (up to 42% efficiency in cortex), liver (up to 46%) and heart (up to 11%). We apply these systems to install putative protective mutations in vivo for Alzheimer's disease in astrocytes and for coronary artery disease in hepatocytes. In vivo prime editing with v3em PE-AAV caused no detectable off-target effects or significant changes in liver enzymes or histology. Optimized PE-AAV systems support the highest unenriched levels of in vivo prime editing reported to date, facilitating the study and potential treatment of diseases with a genetic component.

  PublisherOA PDFDOI

• Pyruvate dehydrogenase kinase expression profile is a biomarker for cancer sensitivity to dichloroacetate-mediated growth inhibition

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-09-22 · 3 citations

  preprintOpen access

  Abstract Background Cancer cells favour glycolysis and lactate production over mitochondrial metabolism despite the presence of oxygen (the Warburg effect). Increased pyruvate dehydrogenase kinase (PDK) activity contributes to this glycolytic phenotype. Dichloroacetate (DCA) is a PDK inhibitor with anti-cancer potential that inhibits all four isoforms of PDK but with differing potencies, thus expression of different isoforms may determine sensitivity to DCA. Methods The association of sensitivity to growth inhibition by DCA, on-target effects of DCA and expression of all four isoforms of PDKs in a range of epithelial cancer cell lines was investigated in vitro and in vivo . Results DCA inhibited growth of cancer cells in vivo and in vitro, reduced pyruvate dehydrogenase phosphorylation and reduced lactate production. The magnitude of the effect of DCA on growth was variable and correlated with the PDK expression profiles of the cells, with low expression of PDK3 (highest K i for DCA) conferring the highest sensitivity towards DCA. PDK2 siRNA-knockdown inhibited growth to a similar extent to DCA, whilst PDK3 knockdown significantly increased sensitivity to DCA. Conclusion The PDK expression profile is a potential biomarker for sensitivity to DCA, and should be considered when translating PDK inhibitors into clinical use.

  PublisherOA PDFDOI

• Phage-assisted evolution and protein engineering yield compact, efficient prime editors

  Cell · 2023-08-01 · 269 citations

  articleOpen access

  Prime editing enables a wide variety of precise genome edits in living cells. Here we use protein evolution and engineering to generate prime editors with reduced size and improved efficiency. Using phage-assisted evolution, we improved editing efficiencies of compact reverse transcriptases by up to 22-fold and generated prime editors that are 516-810 base pairs smaller than the current-generation editor PEmax. We discovered that different reverse transcriptases specialize in different types of edits and used this insight to generate reverse transcriptases that outperform PEmax and PEmaxΔRNaseH, the truncated editor used in dual-AAV delivery systems. Finally, we generated Cas9 domains that improve prime editing. These resulting editors (PE6a-g) enhance therapeutically relevant editing in patient-derived fibroblasts and primary human T-cells. PE6 variants also enable longer insertions to be installed in vivo following dual-AAV delivery, achieving 40% loxP insertion in the cortex of the murine brain, a 24-fold improvement compared to previous state-of-the-art prime editors.

  PublisherDOI

• Efficient in vivo base editing via single adeno-associated viruses with size-optimized genomes encoding compact adenine base editors

  Nature Biomedical Engineering · 2022-07-28 · 185 citations

  articleOpen access

  The viral delivery of base editors has been complicated by their size and by the limited packaging capacity of adeno-associated viruses (AAVs). Typically, dual-AAV approaches based on trans-splicing inteins have been used. Here we show that, compared with dual-AAV systems, AAVs with size-optimized genomes incorporating compact adenine base editors (ABEs) enable efficient editing in mice at similar or lower doses. Single-AAV-encoded ABEs retro-orbitally injected in mice led to editing efficiencies in liver (66%), heart (33%) and muscle (22%) tissues that were up to 2.5-fold those of dual-AAV ABE8e, and to a 93% knockdown (on average) of human PCSK9 and of mouse Pcsk9 and Angptl3 in circulation, concomitant with substantial reductions of plasma cholesterol and triglycerides. Moreover, three size-minimized ABE8e variants, each compatible with single-AAV delivery, collectively offer compatibility with protospacer-adjacent motifs for editing approximately 82% of the adenines in the human genome. ABEs encoded within single AAVs will facilitate research and therapeutic applications of base editing by simplifying AAV production and characterization, and by reducing the dose required for the desired level of editing.

  PublisherOA PDFDOI

• In vivo base editing rescues cone photoreceptors in a mouse model of early-onset inherited retinal degeneration

  Nature Communications · 2022-04-05 · 93 citations

  articleOpen access

  Leber congenital amaurosis (LCA) is the most common cause of inherited retinal degeneration in children. LCA patients with RPE65 mutations show accelerated cone photoreceptor dysfunction and death, resulting in early visual impairment. It is therefore crucial to develop a robust therapy that not only compensates for lost RPE65 function but also protects photoreceptors from further degeneration. Here, we show that in vivo correction of an Rpe65 mutation by adenine base editor (ABE) prolongs the survival of cones in an LCA mouse model. In vitro screening of ABEs and sgRNAs enables the identification of a variant that enhances in vivo correction efficiency. Subretinal delivery of ABE and sgRNA corrects up to 40% of Rpe65 transcripts, restores cone-mediated visual function, and preserves cones in LCA mice. Single-cell RNA-seq reveals upregulation of genes associated with cone phototransduction and survival. Our findings demonstrate base editing as a potential gene therapy that confers long-lasting retinal protection.

  PublisherOA PDFDOI

• Engineered virus-like particles for efficient in vivo delivery of therapeutic proteins

  Cell · 2022 · 615 citations

  1st authorCorresponding
  • Biology
  • Computational biology
  • Cell biology

  Methods to deliver gene editing agents in vivo as ribonucleoproteins could offer safety advantages over nucleic acid delivery approaches. We report the development and application of engineered DNA-free virus-like particles (eVLPs) that efficiently package and deliver base editor or Cas9 ribonucleoproteins. By engineering VLPs to overcome cargo packaging, release, and localization bottlenecks, we developed fourth-generation eVLPs that mediate efficient base editing in several primary mouse and human cell types. Using different glycoproteins in eVLPs alters their cellular tropism. Single injections of eVLPs into mice support therapeutic levels of base editing in multiple tissues, reducing serum Pcsk9 levels 78% following 63% liver editing, and partially restoring visual function in a mouse model of genetic blindness. In vitro and in vivo off-target editing from eVLPs was virtually undetected, an improvement over AAV or plasmid delivery. These results establish eVLPs as promising vehicles for therapeutic macromolecule delivery that combine key advantages of both viral and nonviral delivery.

  PublisherDOI

Frequent coauthors

• David R. Liu

  Howard Hughes Medical Institute

  40 shared

• Aditya Raguram

  Whitehead Institute for Biomedical Research

  31 shared

• Jessie R. Davis

  University College Dublin

  29 shared

• Peyton B. Randolph

  Howard Hughes Medical Institute

  27 shared

• Gregory A. Newby

  Howard Hughes Medical Institute

  21 shared

• Ashutosh Chilkoti

  Duke University

  19 shared

• Meirui An

  Broad Institute

  19 shared

• Xinghai Li

  Duke University

  17 shared

Education

• Ph.D., Materials Science and Engineering

  Boston University

  2015

• M.S., Materials Science and Engineering

  University of California, Santa Barbara

  2010

• B.S., Materials Science and Engineering

  University of California, Santa Barbara

  2009

Awards & honors

• MIT Technological Review 35 Innovators Under 35
• Pratt-Gardner Graduate Fellowship