# Characterization of an anti-Human Papillomavirus (HPV) agent

> **NIH VA I01** · RLR VA MEDICAL CENTER · 2021 · —

## Abstract

Despite the advent of effective anti-Human Papillomavirus (HPV) vaccines, there are no biological agents to
reliably prevent ~80 million Americans from transmitting their infectious HPV viral particles to sexual partners.
 Earlier we determined that the post-translational homocysteinylation of an mRNA-binding protein
(heterogenous nuclear ribonucleoprotein-E1, hnRNP-E1) can transform hnRNP-E1 into a moiety with high
affinity for a HPV16 57-nucleotide (nt) RNA cis-element under conditions of folate deficiency; this interaction
led to a profound inhibition of both HPV16 L1 and L2 viral capsid proteins that are essential for HPV16-
encapsidation (and infectivity). We have patented a powerful mutant of hnRNP-E1 [DomPos-E1(C293S)] that
functions like homocysteinylated-hnRNP-E1 under folate-replete conditions. Because DomPos-E1(C293S)] has
such a strong likelihood to eliminate HPV16 viral capsid proteins and thereby function as an anti-HPV agent, we
wish to test its therapeutic potential both in vitro and in our novel HPV16-xenograft model in Beige Nude mice.
 In Specific Aim 1 we will compare effects of the interaction of DomPos-E1(C293S)-protein [relative to
control wild-type(wt)-like-E1(G292A)-proteins] with HPV16 57-nt cis-element in eliminating HPV16 L1 and L2
viral capsid protein expression. We will also extend these studies to assess the interaction of DomPos-E1(C293S)
with similar cis-elements from low risk HPV6 and 11 and high-risk types (HPV18, 31, 33, 45, 52, 58). Next, we
will confirm the greater impact of DomPos-E1(C293S)- over control wt-like-E1(G292A)- expression in reducing
HPV16 L1 and L2 after stable transduction into HPV16-harboring keratinocytes that are also transformed into
HPV16-organotypic rafts; then we can evaluate the extent in reduction of infectious HPV16 viral particles in 18-
day old rafts and whether there is any increase in genomic integration by amplified capsid-less HPV16 episomes.
 In Specific Aim 2, we will subcutaneously implant these DomPos-E1(C293S)- or control wt-like-
E1(G292A))- expressing rafts in Beige Nude mice using our recently published model. This will allow us to assess
the relative effects of DomPos-E1(C293S)- over control wt-like-E1(G292A) in reducing both HPV16 viral capsid
proteins and infectious viral particles of HPV16 over the ensuing 8 weeks in vivo; evaluating if this reduces the
capacity of the implanted HPV16-raft to auto-infect itself; determining changes in genomic integration by
amplified capsid-less HPV16 episomes; and in prolonging the expected time of rafts to develop HPV16-cancers.
 In Specific Aim 3, we will determine if DomPos-E1(C293S) is significantly more effective than control wt-
like-E1(G292A) in preventing transmission of HPV16 to adjacent tissue. We will adapt our in vivo model to assess
HPV16-infectivity wherein the effectiveness of transmission of infectious HPV16 from one donor tissue to an
uninfected recipient tissue is assessed over 8 weeks in Beige Nude mice.
 These st...

## Key facts

- **NIH application ID:** 10140123
- **Project number:** 5I01BX004932-02
- **Recipient organization:** RLR VA MEDICAL CENTER
- **Principal Investigator:** Asok Antony
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10140123

## Citation

> US National Institutes of Health, RePORTER application 10140123, Characterization of an anti-Human Papillomavirus (HPV) agent (5I01BX004932-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10140123. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*