Molecular Survival Strategies Against Kidney Filtration: Implications for Therapeutic Protein Engineering.

William P Heaps, Anne Elise Packard, Kristina M McCammon, Tyler P Green, Joseph P Talley, Bradley C Bundy, Dennis Della Corte

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In one paragraph

Article in Biophysica, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it

0cells of the map it votes in

0citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

William P HeapsDepartment of Physics and Astronomy, Brigham Young University, Provo, UT 84602, USA.

Anne Elise PackardDepartment of Physics and Astronomy, Brigham Young University, Provo, UT 84602, USA.

Kristina M McCammonDepartment of Physics and Astronomy, Brigham Young University, Provo, UT 84602, USA.

Tyler P GreenDepartment of Chemical and Biological Engineering, Brigham Young University, Provo, UT 84602, USA.

Joseph P TalleyDepartment of Chemical and Biological Engineering, Brigham Young University, Provo, UT 84602, USA.

Bradley C BundyDepartment of Chemical and Biological Engineering, Brigham Young University, Provo, UT 84602, USA.

Dennis Della CorteDepartment of Physics and Astronomy, Brigham Young University, Provo, UT 84602, USA.

Funding

NIGMS NIH HHS R15 GM155803

6 · The paper itself

Abstract

The glomerular filtration barrier poses a significant challenge for circulating proteins, with molecules below ~60-70 kDa facing rapid renal clearance. Endogenous proteins have evolved sophisticated evasion mechanisms including oligomerization, carrier binding, electrostatic repulsion, and FcRn-mediated recycling. Understanding these natural strategies provides blueprints for engineering therapeutic proteins with improved pharmacokinetics. This review examines how endogenous proteins resist filtration, evaluates their application in protein engineering, and discusses clinical translation including established technologies (PEGylation, Fc-fusion) and emerging strategies (albumin-binding domains, glycoengineering). We address critical challenges of balancing half-life extension with tissue penetration, biological activity, and immunogenicity-essential considerations for the rational design of next-generation therapeutics with optimized dosing and enhanced efficacy.

Indexed as

albumin bindingFc-fusionFcRn recyclingglomerular filtrationhalf-life extensionPEGylationpharmacokineticsprotein therapeutics

Identifiers

PMID42524171

DOI10.3390/biophysica6010004

PMCPMC13410728

What Socratic holds

Textmetadata

LicenceCC BY

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.